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1.  The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation 
Pereyra, Florencia | Jia, Xiaoming | McLaren, Paul J. | Telenti, Amalio | de Bakker, Paul I.W. | Walker, Bruce D. | Jia, Xiaoming | McLaren, Paul J. | Ripke, Stephan | Brumme, Chanson J. | Pulit, Sara L. | Telenti, Amalio | Carrington, Mary | Kadie, Carl M. | Carlson, Jonathan M. | Heckerman, David | de Bakker, Paul I.W. | Pereyra, Florencia | de Bakker, Paul I.W. | Graham, Robert R. | Plenge, Robert M. | Deeks, Steven G. | Walker, Bruce D. | Gianniny, Lauren | Crawford, Gabriel | Sullivan, Jordan | Gonzalez, Elena | Davies, Leela | Camargo, Amy | Moore, Jamie M. | Beattie, Nicole | Gupta, Supriya | Crenshaw, Andrew | Burtt, Noël P. | Guiducci, Candace | Gupta, Namrata | Carrington, Mary | Gao, Xiaojiang | Qi, Ying | Yuki, Yuko | Pereyra, Florencia | Piechocka-Trocha, Alicja | Cutrell, Emily | Rosenberg, Rachel | Moss, Kristin L. | Lemay, Paul | O’Leary, Jessica | Schaefer, Todd | Verma, Pranshu | Toth, Ildiko | Block, Brian | Baker, Brett | Rothchild, Alissa | Lian, Jeffrey | Proudfoot, Jacqueline | Alvino, Donna Marie L. | Vine, Seanna | Addo, Marylyn M. | Allen, Todd M. | Altfeld, Marcus | Henn, Matthew R. | Le Gall, Sylvie | Streeck, Hendrik | Walker, Bruce D. | Haas, David W. | Kuritzkes, Daniel R. | Robbins, Gregory K. | Shafer, Robert W. | Gulick, Roy M. | Shikuma, Cecilia M. | Haubrich, Richard | Riddler, Sharon | Sax, Paul E. | Daar, Eric S. | Ribaudo, Heather J. | Agan, Brian | Agarwal, Shanu | Ahern, Richard L. | Allen, Brady L. | Altidor, Sherly | Altschuler, Eric L. | Ambardar, Sujata | Anastos, Kathryn | Anderson, Ben | Anderson, Val | Andrady, Ushan | Antoniskis, Diana | Bangsberg, David | Barbaro, Daniel | Barrie, William | Bartczak, J. | Barton, Simon | Basden, Patricia | Basgoz, Nesli | Bazner, Suzane | Bellos, Nicholaos C. | Benson, Anne M. | Berger, Judith | Bernard, Nicole F. | Bernard, Annette M. | Birch, Christopher | Bodner, Stanley J. | Bolan, Robert K. | Boudreaux, Emilie T. | Bradley, Meg | Braun, James F. | Brndjar, Jon E. | Brown, Stephen J. | Brown, Katherine | Brown, Sheldon T. | Burack, Jedidiah | Bush, Larry M. | Cafaro, Virginia | Campbell, Omobolaji | Campbell, John | Carlson, Robert H. | Carmichael, J. Kevin | Casey, Kathleen K. | Cavacuiti, Chris | Celestin, Gregory | Chambers, Steven T. | Chez, Nancy | Chirch, Lisa M. | Cimoch, Paul J. | Cohen, Daniel | Cohn, Lillian E. | Conway, Brian | Cooper, David A. | Cornelson, Brian | Cox, David T. | Cristofano, Michael V. | Cuchural, George | Czartoski, Julie L. | Dahman, Joseph M. | Daly, Jennifer S. | Davis, Benjamin T. | Davis, Kristine | Davod, Sheila M. | Deeks, Steven G. | DeJesus, Edwin | Dietz, Craig A. | Dunham, Eleanor | Dunn, Michael E. | Ellerin, Todd B. | Eron, Joseph J. | Fangman, John J.W. | Farel, Claire E. | Ferlazzo, Helen | Fidler, Sarah | Fleenor-Ford, Anita | Frankel, Renee | Freedberg, Kenneth A. | French, Neel K. | Fuchs, Jonathan D. | Fuller, Jon D. | Gaberman, Jonna | Gallant, Joel E. | Gandhi, Rajesh T. | Garcia, Efrain | Garmon, Donald | Gathe, Joseph C. | Gaultier, Cyril R. | Gebre, Wondwoosen | Gilman, Frank D. | Gilson, Ian | Goepfert, Paul A. | Gottlieb, Michael S. | Goulston, Claudia | Groger, Richard K. | Gurley, T. Douglas | Haber, Stuart | Hardwicke, Robin | Hardy, W. David | Harrigan, P. Richard | Hawkins, Trevor N. | Heath, Sonya | Hecht, Frederick M. | Henry, W. Keith | Hladek, Melissa | Hoffman, Robert P. | Horton, James M. | Hsu, Ricky K. | Huhn, Gregory D. | Hunt, Peter | Hupert, Mark J. | Illeman, Mark L. | Jaeger, Hans | Jellinger, Robert M. | John, Mina | Johnson, Jennifer A. | Johnson, Kristin L. | Johnson, Heather | Johnson, Kay | Joly, Jennifer | Jordan, Wilbert C. | Kauffman, Carol A. | Khanlou, Homayoon | Killian, Robert K. | Kim, Arthur Y. | Kim, David D. | Kinder, Clifford A. | Kirchner, Jeffrey T. | Kogelman, Laura | Kojic, Erna Milunka | Korthuis, P. Todd | Kurisu, Wayne | Kwon, Douglas S. | LaMar, Melissa | Lampiris, Harry | Lanzafame, Massimiliano | Lederman, Michael M. | Lee, David M. | Lee, Jean M.L. | Lee, Marah J. | Lee, Edward T.Y. | Lemoine, Janice | Levy, Jay A. | Llibre, Josep M. | Liguori, Michael A. | Little, Susan J. | Liu, Anne Y. | Lopez, Alvaro J. | Loutfy, Mono R. | Loy, Dawn | Mohammed, Debbie Y. | Man, Alan | Mansour, Michael K. | Marconi, Vincent C. | Markowitz, Martin | Marques, Rui | Martin, Jeffrey N. | Martin, Harold L. | Mayer, Kenneth Hugh | McElrath, M. Juliana | McGhee, Theresa A. | McGovern, Barbara H. | McGowan, Katherine | McIntyre, Dawn | Mcleod, Gavin X. | Menezes, Prema | Mesa, Greg | Metroka, Craig E. | Meyer-Olson, Dirk | Miller, Andy O. | Montgomery, Kate | Mounzer, Karam C. | Nagami, Ellen H. | Nagin, Iris | Nahass, Ronald G. | Nelson, Margret O. | Nielsen, Craig | Norene, David L. | O’Connor, David H. | Ojikutu, Bisola O. | Okulicz, Jason | Oladehin, Olakunle O. | Oldfield, Edward C. | Olender, Susan A. | Ostrowski, Mario | Owen, William F. | Pae, Eunice | Parsonnet, Jeffrey | Pavlatos, Andrew M. | Perlmutter, Aaron M. | Pierce, Michael N. | Pincus, Jonathan M. | Pisani, Leandro | Price, Lawrence Jay | Proia, Laurie | Prokesch, Richard C. | Pujet, Heather Calderon | Ramgopal, Moti | Rathod, Almas | Rausch, Michael | Ravishankar, J. | Rhame, Frank S. | Richards, Constance Shamuyarira | Richman, Douglas D. | Robbins, Gregory K. | Rodes, Berta | Rodriguez, Milagros | Rose, Richard C. | Rosenberg, Eric S. | Rosenthal, Daniel | Ross, Polly E. | Rubin, David S. | Rumbaugh, Elease | Saenz, Luis | Salvaggio, Michelle R. | Sanchez, William C. | Sanjana, Veeraf M. | Santiago, Steven | Schmidt, Wolfgang | Schuitemaker, Hanneke | Sestak, Philip M. | Shalit, Peter | Shay, William | Shirvani, Vivian N. | Silebi, Vanessa I. | Sizemore, James M. | Skolnik, Paul R. | Sokol-Anderson, Marcia | Sosman, James M. | Stabile, Paul | Stapleton, Jack T. | Starrett, Sheree | Stein, Francine | Stellbrink, Hans-Jurgen | Sterman, F. Lisa | Stone, Valerie E. | Stone, David R. | Tambussi, Giuseppe | Taplitz, Randy A. | Tedaldi, Ellen M. | Telenti, Amalio | Theisen, William | Torres, Richard | Tosiello, Lorraine | Tremblay, Cecile | Tribble, Marc A. | Trinh, Phuong D. | Tsao, Alice | Ueda, Peggy | Vaccaro, Anthony | Valadas, Emilia | Vanig, Thanes J. | Vecino, Isabel | Vega, Vilma M. | Veikley, Wenoah | Wade, Barbara H. | Walworth, Charles | Wanidworanun, Chingchai | Ward, Douglas J. | Warner, Daniel A. | Weber, Robert D. | Webster, Duncan | Weis, Steve | Wheeler, David A. | White, David J. | Wilkins, Ed | Winston, Alan | Wlodaver, Clifford G. | Wout, Angelique van’t | Wright, David P. | Yang, Otto O. | Yurdin, David L. | Zabukovic, Brandon W. | Zachary, Kimon C. | Zeeman, Beth | Zhao, Meng
Science (New York, N.Y.)  2010;330(6010):1551-1557.
Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.
doi:10.1126/science.1195271
PMCID: PMC3235490  PMID: 21051598
2.  HIV-1 control by NK cells via reduced interaction between KIR2DL2 and HLA-C*12:02/C*14:03 
Cell reports  2016;17(9):2210-2220.
SUMMARY
Natural killer (NK) cells control viral infection in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands. We investigated 504 ART-free Japanese patients chronically infected with HIV-1 and identified two KIR/HLA combinations, KIR2DL2/HLA-C*12:02 and KIR2DL2/HLA-C*14:03, that impact suppression of HIV-1 replication. KIR2DL2+ NK cells suppressed viral replication in HLA-C*14:03+ or HLA-C*12:02+ cells to a significantly greater extent than did KIR2DL2− NK cells in vitro. Functional analysis showed that the binding between HIV-1-derived peptide and HLA-C*14:03 or HLA-C*12:02 influenced KIR2DL2+NK cell activity through reduced expression of the peptide-HLA (pHLA) complex on the cell surface (i.e. reduced KIR2DL2 ligand expression), rather than through reduced binding affinity of KIR2DL2 to the respective pHLA complexes. Thus, KIR2DL2/HLA-C*12:02 and KIR2DL2/HLA-C*14:03 compound genotypes have protective effects on control of HIV-1 through a mechanism involving KIR2DL2-mediated NK cell recognition of virus-infected cells, providing additional understanding of NK cells in HIV-1 infection.
Graphical Abstract
doi:10.1016/j.celrep.2016.10.075
PMCID: PMC5184766  PMID: 27880898
3.  Unique human immune signature of Ebola virus disease in Guinea 
Ruibal, Paula | Oestereich, Lisa | Lüdtke, Anja | Becker-Ziaja, Beate | Wozniak, David M. | Kerber, Romy | Korva, Miša | Cabeza-Cabrerizo, Mar | Bore, Joseph A. | Koundouno, Fara Raymond | Duraffour, Sophie | Weller, Romy | Thorenz, Anja | Cimini, Eleonora | Viola, Domenico | Agrati, Chiara | Repits, Johanna | Afrough, Babak | Cowley, Lauren A | Ngabo, Didier | Hinzmann, Julia | Mertens, Marc | Vitoriano, Inês | Logue, Christopher H. | Boettcher, Jan Peter | Pallasch, Elisa | Sachse, Andreas | Bah, Amadou | Nitzsche, Katja | Kuisma, Eeva | Michel, Janine | Holm, Tobias | Zekeng, Elsa-Gayle | García-Dorival, Isabel | Wölfel, Roman | Stoecker, Kilian | Fleischmann, Erna | Strecker, Thomas | Di Caro, Antonino | Avšič-Županc, Tatjana | Kurth, Andreas | Meschi, Silvia | Mély, Stephane | Newman, Edmund | Bocquin, Anne | Kis, Zoltan | Kelterbaum, Anne | Molkenthin, Peter | Carletti, Fabrizio | Portmann, Jasmine | Wolff, Svenja | Castilletti, Concetta | Schudt, Gordian | Fizet, Alexandra | Ottowell, Lisa J. | Herker, Eva | Jacobs, Thomas | Kretschmer, Birte | Severi, Ettore | Ouedraogo, Nobila | Lago, Mar | Negredo, Anabel | Franco, Leticia | Anda, Pedro | Schmiedel, Stefan | Kreuels, Benno | Wichmann, Dominic | Addo, Marylyn M. | Lohse, Ansgar W. | De Clerck, Hilde | Nanclares, Carolina | Jonckheere, Sylvie | Van Herp, Michel | Sprecher, Armand | Xiaojiang, Gao | Carrington, Mary | Miranda, Osvaldo | Castro, Carlos M. | Gabriel, Martin | Drury, Patrick | Formenty, Pierre | Diallo, Boubacar | Koivogui, Lamine | Magassouba, N’Faly | Carroll, Miles W. | Günther, Stephan | Muñoz-Fontela, César
Nature  2016;533(7601):100-104.
Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus (EBOV)2,3. Here, we have for the first time evaluated the physiology of the human T cell immune response in EVD patients at the time of admission at the Ebola Treatment Center (ETC) in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we have identified an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by high percentage of CD4 and CD8 T cells expressing the inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1), which was correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation despite comparable overall T cell activation. Concommittant with virus clearance, survivors mounted a robust EBOV-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
doi:10.1038/nature17949
PMCID: PMC4876960  PMID: 27147028
4.  7th drug hypersensitivity meeting: part one 
Carr, Daniel F. | Chung, Wen-Hung | Jenkiins, Rosalind E. | Chaponda, Mas | Nwikue, Gospel | Cornejo Castro, Elena M. | Antoine, Daniel J. | Pirmohamed, Munir | Wuillemin, Natascha | Dina, Dolores | Eriksson, Klara K. | Yerly, Daniel | Pavlos, Rebecca | Mckinnin, Elizabeth | Ostrov, David | Peters, Bjoern | Buus, Soren | Koelle, David | Chopra, Abha | Rive, Craig | Redwood, Alec | Restrepo, Susana | Bracey, Austin | Yuan, Jing | Gaudieri, Silvana | Carrington, Mary | Haas, David | Mallal, Simon | Phillips, Elizabeth | De Boer, Douwe | Menheere, Paul | Nieuwhof, Chris | Bons, Judith | Jonsson, Friederike | De Chaisemartin, Luc | Granger, Vanessa | Gillis, Caitlin | Gouel, Aurelie | Neukirch, Catherine | Dib, Fadia | Nicaise, Pascale Roland | Longrois, Dan | Tubach, Florence | Martin, Sylvie | Bruhns, Pierre | Chen, Kai-Lung | Liao, Shu-Ling | Sheen, Yi-Shuan | Cho, Yung-Tsu | Yang, Che-Wen | Liau, Jau-Yu | Chu, Chia-Yu | Aguiar, Rita | Lopes, Anabela | Fernandes, Natália | Viegas, Leonor | Pereira-Barbosa, M. A. | Bünter, Antonia | Gupta, Nisha | Petkovic, Tatjana Pecaric | Wirth, Nicole | Pichler, Werner J. | Hausmann, Oliver | Yazicioglu, Mehtap | Ozdemir, Pinar G. | Ciplak, Gokce | Kaya, Ozkan | Cooke, Peter John | Mota, Inês | Gaspar, Ângela | Benito-Garcia, Filipe | Chambel, Marta | Morais-Almeida, Mário | Marques, Luis | Alcoceba, Eva | Lara, Silvia | Carneiro-Leão, Leonor | Botelho, Carmen | Dias-Castro, Eunice | Cernadas, Josefina R. | Nicholls, Katherine | Lay, William | Smith, Olivia | Collins, Christine | Unglik, Gary | Spriggs, Kymble | Auyeung, Priscilla | McComish, Jeremy | Douglass, Jo A. | Peter, Jonny G. | Potter, Paul | Carolino, Fabrícia | De Castro, Eunice Dias | Moreira, Ana Sofia | Abreu, Carmo | Gomes, Eva | Cardoso, Bárbara Kong | Tomaz, Elza | Correia, Sara | Inácio, Filipe | Arnold, Annabelle | Bear, Natasha | Rueter, Kristina | Gong, Grace | O’Sullivan, Michael | Muthusamy, Saravanan | Noble, Valerie | Lucas, Michaela | Buterleviciute, Neringa | Rudzeviciene, Odilija | Abreu, Carmo | May, Sara | Pongdee, Thanai | Park, Miguel | Griguola, Linas | Vinikovas, Arturas | Kašinskaite, Simona | Kvedariene, Violeta | Aktas, Ayse | Rahman, Suheyla | Elbi, Huseyin | Ozyurt, Beyhan Cengiz | Cavkaytar, Ozlem | Karaatmaca, Betul | Cetinkaya, Pinar Gur | Esenboga, Saliha | Sahiner, Umit M. | Sekerel, Bulent E. | Soyer, Ozge | Zubrinich, Celia | Tong, Bianca | Patel, Mittal | Giles, Michelle | O’Hehir, Robyn | Puy, Robert | Amaral, Luís | Demir, Semra | Gelincik, Asli | Olgac, Muge | Caskun, Raif | Unal, Derya | Colakoglu, Bahauddin | Buyukozturk, Suna | Matute, Olga Vega | Bernad, Amalia | Gastaminza, Gabriel | Madamba, Roselle | Lacasa, Carlos | Goikoetxea, M. J. | D’Amelio, Carmen | Rifón, Jose | Martínez, Nicolas | Ferrer, Marta | Ribeiro, Carmelita | Faria, Emília | Frutuoso, Cristina | Barros, Anabela | Lebre, Rosário | Pego, Alice | Bom, Ana Todo | Ensina, Luis Felipe | Aranda, Carolina | Nunes, Ines Camelo | Martins, Ana Maria | Solé, Dirceu | Bavbek, Sevim | Kendirlinan, Resat | Çerçi, Pamir | Tutluer, Seda | Soyyigit, Sadan | Sözener, Zeynep Çelebi | Aydin, Ömür | Gümüsburun, Reyhan | Almeida, Marta | Sai, Kimie | Imatoh, Takuya | Nakamura, Ryosuke | Fukazawa, Chisato | Hinomura, Yasushi | Saito, Yoshiro | Sousa-Pinto, Bernardo | Correia, Cláudia | Gomes, Lídia | Gil-Mata, Sara | Araújo, Luís | Delgado, Luís | Sai, Kimie | Okamoto-Uchida, Yoshimi | Kajinami, Koji | Matsunaga, Kayoko | Aihara, Michiko | Wang, Chuang-Wei | Su, Shih-Chi | Hung, Shuen-Iu | Ho, Hsin-Chun | Yang, Chih-Hsun | Paulmann, Maren | Dunant, Ariane | Mockenhaupt, Maja | Sekula, Peggy | Schumacher, Martin | Kardaun, Sylvia | Naldi, Luigi | Bellón, Teresa | Creamer, Daniel | Haddad, Cynthia | Sassolas, Bruno | Lebrun-Vignes, Bénédicte | Valeyrie-Allanore, Laurence | Roujeau, Jean-Claude | Paulmann, Maren | Kremmler, Carmen | Mockenhaupt, Maja | Dodiuk-Gad, Roni P. | Olteanu, Cristina | Feinstein, Anthony | Hashimoto, Rena | Alhusayen, Raed | Whyte-Croasdaile, Sonia | Finkelstein, Yaron | Burnett, Marjorie | Sade, Shachar | Cartotto, Robert | Jeschke, Marc | Shear, Neil H. | Takamura, Naoko | Yamane, Yumiko | Matsukura, Setsuko | Nakamura, Kazuko | Watanabe, Yuko | Yamaguchi, Yukie | Kambara, Takeshi | Ikezawa, Zenro | Aihara, Michiko | Hashimoto, Rena | Chew, Hall | Burnett, Marjorie | Jeschke, Marc | Knezevic, Brittany | Ionmhain, Una Nic | Barraclough, Allison | Anstey, Matthew | Usui, Toru | Meng, Xiaoli | Farrell, John | Whitaker, Paul | Watson, John | French, Neil | Park, Kevin | Naisbitt, Dean | Neves, Ana Castro | Cadinha, Susana | Moreira, Ana | Da Silva, J. P. Moreira | Drvar, Daniela Ledic | Gulin, Sandra Jerkovic | Hadzavdic, Suzana Ljubojevic | Ceovic, Romana | De Francisco, Ana Montoro | De Vicente Jiménez, Talía | Luque, Amelia García | David, Natalia Rosado | Galván, José Mª Mateos | Darlenski, Razvigor | Gulin, Dario | Sikic, Jozica | Habek, Jasna Cerkez | Galic, Edvard | Specht, Philip | Staab, Doris | Mayer, Beate | Roehmel, Jobst | Solovan, Caius | Chiriac, Anca | Djurinec, Paola | Kostovic, Kresimir | Bradamante, Mirna | Almeida, Jose Pedro | Caiado, Joana | Pedro, Elisa | Da Silva, Pedro Canas | Barbosa, Manuel Pereira | Bogas, Gador | Blanca-López, Natalia | Pérez-Alzate, Diana | Doña, Inmaculada | Agúndez, José Augusto | García-Martín, Elena | Cornejo-García, José Antonio | Mayorga, Cristobalina | Torres, María José | Canto, Maria Gabriela | Blanca, Miguel | Aksakal, Sengül | Sin, Aytül Zerrin | Koç, Zeynep Peker | Günsen, Fatma Düsünür | Ardeniz, Ömür | Gökmen, Emine Nihal Mete | Gülbahar, Okan | Kokuludag, Ali | Pérez-Sánchez, Natalia | Salas, María | Salas, Maria | Gomez, Francisca | Barrionuevo, Esther | Andreu, Inmaculada | Miranda, Miguel Ángel | Didžiokaite, Gabija | Gaidej, Olesia | Kašinskaite, Simona | Garcimartin, Maria Isabel | Somoza, Maria Luisa | Bojas, Gador | Cornejo-Garcia, Jose Antonio | Perez, Francisco Javier Ruano | Miranda, Miguel Angel | Jerschow, Elina | Pelletier, Teresa | Ren, Zhen | Hudes, Golda | Sanak, Marek | Morales, Esperanza | Schuster, Victor | Spivack, Simon D | Rosenstreich, David | Erzen, Renato | Silar, Mira | Bajrovic, Nissera | Rijavec, Matija | Zidarn, Mihaela | Korosec, Peter | Castro, Eunice | Al-Ahmad, Mona | Rodriguez, Tito | Azevedo, João Pedro | Tavares, Beatriz | Regateiro, Frederico | Todo-Bom, Ana | Miranda, Pablo Andrés | De La Cruz Hoyos, Bautista | Abuzeid, Waleed | Akbar, Nadeem | Gibber, Marc | Fried, Marvin | Han, Weiguo | Keskin, Taha | Tamayev, Robert | Spivack, Simon D. | Rosenstreich, David | Jerschow, Elina | Boni, Elisa | Russello, Marina | Mauro, Marina | Neto, Marta Ferreira | Brosseron, Lise | Malheiro, Daniela | Barreira, Patrícia | Sprigg, Dustin | Trevenen, Michelle | Seet, Jason | Trubiano, Jason | Smith, William | Jeelall, Yogesh | Vale, Sandra | Loh, Richard | Mclean-Tooke, Andrew | Müller, Sabine | Amstutz, Ursula | Jörg, Lukas | Yawalkar, Nikhil | Krähenbühl, Stephan | Leblanc, Ana | Ribeiro, Laura | Vega, Arantza | Rivas, Raquel Gutierrez | Alonso, Ana | Beitia, Juan Maria | Mateo, Belén | Cárdenas, Remedios | Garcia-Dominguez, Juan Jesus | Pavlos, Rebecca | Strautins, Kaija | James, Ian | Mallal, Simon | Redwood, Alec | Aguiar, Rita | Lopes, Anabela | Neves, Ana | Do Céu Machado, Maria | Dalgiç, Ceyda Tunakan | Gökmen, Emine Nihal Mete | Bulut, Gökten | Ardeniz, Fatma Ömür | Gülbahar, Okan | Sin, Aytül Zerrin | Hsu, Shao-Hsuan | Yang, Che-Wen | Ye, Young-Min | Hur, Gyu-Young | Park, Hae-Sim | Kim, Seung-Hyun | Ali, Syed | Hollingsworth, Peter N. | Mclean-Tooke, Andrew P. C. | Chadly, Zohra | Fredj, Nadia Ben | Aouam, Karim | Romdhane, Haifa Ben | Boughattas, Naceur A. | Chaabane, Amel | Salazar, Marina Lluncor | Pola, Beatriz | Fiandor, Ana | Ramírez, Elena | Ortega, Javier Domínguez | Quirce, Santiago | Cabañas, Rosario | Baynova, Krasimira | Labella, Marina | Prados, Manuel | Ramonaite, Agne | Bajoriuniene, Ieva | Sitkauskiene, Brigita | Sakalauskas, Raimundas | Kwon, Jae-Woo | Park, Shinyoung | Silva, Diana | Leão, Leonor Carneiro | Castro, Eunice | Garcimartin, Maria | De La Torre, Maria Vazquez | Pérez, Francisco Javier Ruano | Haroun, Elisa | Diez, Gabriela Canto | Ónodi-Nagy, Katinka | Kinyó, Ágnes | Kemény, Lajos | Bata-Csörgo, Zsuzsanna | Pita, Joana Sofia | Fernandes, Rosa Anita | Moura, Ana | Sousa, Nuno | Loureiro, Carlos | Pfützner, Wolfgang | Marrouche, Nadine | Grattan, Clive | Chen, Yu-En | Chen, Chun-Bing | Hsiao, Yu-Ping | Garcimartin, Maria Isabel | Ruano, Francisco Javier
Table of contents
Oral Abstracts
O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN
Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed
O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture?
Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly
O3 Specific binding characteristics of HLA alleles associated with nevirapine hypersensitivity
Rebecca Pavlos, Elizabeth Mckinnin, David Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Jing Yuan, Silvana Gaudieri, Mary Carrington, David Haas, Simon Mallal, Elizabeth Phillips
O4 Do we need to measure total ige for the interpretation of analytical results of ImmunoCAP dnd 3gAllergy specific IgE?
Douwe De Boer, Paul Menheere, Chris Nieuwhof, Judith Bons
O5 Neutrophil activation in systemic anaphylaxis: results from the multicentric NASA study
Friederike Jonsson, Luc De Chaisemartin, Vanessa Granger, Caitlin Gillis, Aurelie Gouel, Catherine Neukirch, Fadia Dib, Pascale Roland Nicaise, Dan Longrois, Florence Tubach, Sylvie Martin, Pierre Bruhns, NASA Study Group
O6 Purpuric drug eruptions due to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small-cell lung cancer (NSCLC): a clinic-pathological study of 32 cases
Kai-Lung Chen, Shu-Ling Liao, Yi-Shuan Sheen, Yung-Tsu Cho, Che-Wen Yang, Jau-Yu Liau, Chia-Yu Chu
Poster presentations: Poster Walk 1—Anaphylaxis (P01–P09)
P1 Anaphylactic reactions during anaesthesia and the perioperative period
Rita Aguiar, Anabela Lopes, Natália Fernandes, Leonor Viegas, M. A. Pereira-Barbosa
P2 Anaphylaxis to chlorhexidine: is there a cross-reactivity to alexidine?
Antonia Bünter, Nisha Gupta, Tatjana Pecaric Petkovic, Nicole Wirth, Werner J. Pichler, Oliver Hausmann
P3 Cefotaxime-induced severe anaphylaxis in a neonate
Mehtap Yazicioglu, Pinar G. Ozdemir, Gokce Ciplak, Ozkan Kaya
P4 Clinical features and diagnosis of anaphylaxis resulting from exposure to chlorhexidine
Peter John Cooke
P5 Drug-induced anaphylaxis: five-year single-center survey
Inês Mota, Ângela Gaspar, Filipe Benito-Garcia, Marta Chambel, Mário Morais-Almeida
P6 Intraoperative severe anaphylactic reaction due to patent blue v dye
Luis Marques, Eva Alcoceba, Silvia Lara
P7 Kounis syndrome in the setting of anaphylaxis to diclofenac
Leonor Carneiro-Leão, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas
P8 Perioperative anaphylaxis audit: Royal Melbourne Hospital
Katherine Nicholls, William Lay, Olivia Smith, Christine Collins, Gary Unglik, Kymble Spriggs, Priscilla Auyeung, Jeremy McComish, Jo A. Douglass
P9 Recurrent peri-operative anaphylaxis: a perfect storm
Jonny G. Peter, Paul Potter
Poster Walk 2: DH regions and patient groups (P10–P19)
P10 A rare presentation of amoxicillin allergy in a young child
Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas
P11 Adverse drug reactions in children: antibiotics or virus?
Ana Sofia Moreira, Carmo Abreu, Eva Gomes
P12 Allergic reactions in invasive medical procedures
Bárbara Kong Cardoso, Elza Tomaz, Sara Correia, Filipe Inácio
P13 Antibiotic allergy in children: room for improvement
Annabelle Arnold, Natasha Bear, Kristina Rueter, Grace Gong, Michael O’Sullivan, Saravanan Muthusamy, Valerie Noble, Michaela Lucas
P14 Drug hypersensitivity reactions in children and results of diagnostic evaluation
Neringa Buterleviciute, Odilija Rudzeviciene
P15 Nonimmediate cutaneous drug reactions in children: are skin tests required?
Ana Sofia Moreira, Carmo Abreu, Eva Gomes
P16 Pediatric patients with a history of penicillin allergy and a positive penicillin skin test may not be at an increased risk for multiple drug allergies
Sara May, Thanai Pongdee, Miguel Park
P17 Proved hypersensitivity to drugs according data of Vilnius University Hospital Santariskiu Klinikos
Linas Griguola, Arturas Vinikovas, Simona Kašinskaite, Violeta Kvedariene
P18 Self-reported prevalence of drug hypersensitivity reactions among students in Celal Bayar University, Turkey
Ayse Aktas, Suheyla Rahman, Huseyin Elbi, Beyhan Cengiz Ozyurt
P19 Severe drug hypersensitivity reactions in pediatric age
Ozlem Cavkaytar, Betul Karaatmaca, Pinar Gur Cetinkaya, Saliha Esenboga, Umit M. Sahiner, Bulent E. Sekerel, Ozge Soyer
Poster Walk 3: Desensitisation (P20–P28)
P20 A protocol for desensitisation to valaciclovir
Celia Zubrinich, Bianca Tong, Mittal Patel, Michelle Giles, Robyn O’Hehir, Robert Puy
P21 A rare case of desensitization to modafinil
Josefina Cernadas, Luís Amaral, Fabrícia Carolino
P22 A sixteen-day desensitization protocol in delayed type hypersensitivity reactions to oral drugs
Semra Demir, Asli Gelincik, Muge Olgac, Raif Caskun, Derya Unal, Bahauddin Colakoglu, Suna Buyukozturk
P23 Desensitization to intravenous etoposide using a 12 and a 13-step protocol. Two cases report
Olga Vega Matute, Amalia Bernad, Gabriel Gastaminza, Roselle Madamba, Carlos Lacasa, M. J. Goikoetxea, Carmen D’Amelio, Jose Rifón, Nicolas Martínez, Marta Ferrer
P24 Drug desensitisation in oncology: the experience of an immunoallergology department for 5 years
Carmelita Ribeiro, Emília Faria, Cristina Frutuoso, Anabela Barros, Rosário Lebre, Alice Pego, Ana Todo Bom
P25 Filgrastim anaphylaxis: a successful desensitization protocol
Luis Amaral, Josefina Cernadas
P26 Galsulfase hypersensitivity and desensitization of a mucopolysaccharidosis VI patient
Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Ana Maria Martins, Dirceu Solé
P27 Rapid drug desensitization with biologicals: one-center experience with four biologicals
Sevim Bavbek, Resat Kendirlinan, Pamir Çerçi, Seda Tutluer, Sadan Soyyigit, Zeynep Çelebi Sözener, Ömür Aydin, Reyhan Gümüsburun
P28 Successful desensitization to a high dose of methotrexate in a delayed type hypersensitivity reaction
Josefina Cernadas, Leonor Carneiro-Leão, Fabrícia Carolino, Marta Almeida
Poster Walk 4: SJS (P29–P38)
P29 Assessment of impact of infection on drug-induced severe cutaneous adverse reactions and rhabdomyolysis using the Japanese adverse drug event report database
Kimie Sai, Takuya Imatoh, Ryosuke Nakamura, Chisato Fukazawa, Yasushi Hinomura, Yoshiro Saito
P30 Characterization of erythema multiforme and severe cutaneous adverse reactions hospitalizations
Bernardo Sousa-Pinto, Cláudia Correia, Lídia Gomes, Sara Gil-Mata, Luís Araújo, Luís Delgado
P31 Effects of infection on incidence/severity of SJS/TEN and myopathy in Japanese cases analyzed by voluntary case reports
Ryosuke Nakamura, Kimie Sai, Takuya Imatoh, Yoshimi Okamoto-Uchida, Koji Kajinami, Kayoko Matsunaga, Michiko Aihara, Yoshiro Saito
P32 Efficacy of tumor necrosis factor—a antagonists in Stevens–Johnson syndrome and toxic epidermal necrolysis: a randomized controlled trial and immunosuppressive effects evaluation
Chuang-Wei Wang, Shih-Chi Su, Shuen-Iu Hung, Hsin-Chun Ho, Chih-Hsun Yang, Wen-Hung Chung
P33 Evolution of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis in Europe: analysis of 10 years RegiSCAR-Study
Maren Paulmann, Ariane Dunant, Maja Mockenhaupt, Peggy Sekula, Martin Schumacher, Sylvia Kardaun, Luigi Naldi, Teresa Bellón, Daniel Creamer, Cynthia Haddad, Bruno Sassolas, Bénédicte Lebrun-Vignes, Laurence Valeyrie-Allanore, Jean-Claude Roujeau
P34 Long-term sequelae in patients with Stevens–Johnson syndrome and toxic epidermal necrolysis: a 5-year analysis
Maren Paulmann, Carmen Kremmler, Peggy Sekula, Laurence Valeyrie-Allanore, Luigi Naldi, Sylvia Kardaun, Maja Mockenhaupt
P35 Major emotional complications and decreased health related quality of life among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis
Roni P. Dodiuk-Gad, Cristina Olteanu, Anthony Feinstein, Rena Hashimoto, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear
P36 Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients: treatment and outcome
Naoko Takamura, Yumiko Yamane, Setsuko Matsukura, Kazuko Nakamura, Yuko Watanabe, Yukie Yamaguchi, Takeshi Kambara, Zenro Ikezawa, Michiko Aihara
P37 Severe physical complications among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis
Roni P. Dodiuk-Gad, Cristina Olteanu, Rena Hashimoto, Hall Chew, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear
P38 Stevens–Johnson syndrome/toxic epidermal necrolysis combined with haemophagocytic lymphohistiocytosis: a case report
Brittany Knezevic, Una Nic Ionmhain, Allison Barraclough, Michaela Lucas, Matthew Anstey
Poster Walk 5: Other organs/unexpected immune reactions (P39–P47)
P39 A case report of patient with anti-tuberculosis drug-related severe liver failure
Toru Usui, Xiaoli Meng, John Farrell, Paul Whitaker, John Watson, Neil French, Kevin Park, Dean Naisbitt
P40 Acute interstitial nephritis induced by ibuprofen
Ana Castro Neves, Susana Cadinha, Ana Moreira, J. P. Moreira Da Silva
P41 Cetuximab induced acneiform rash—two case reports
Daniela Ledic Drvar, Sandra Jerkovic Gulin, Suzana Ljubojevic Hadzavdic, Romana Ceovic
P42 Enteropathy associated with losartan
Ana Montoro De Francisco, Talía De Vicente Jiménez, Amelia García Luque, Natalia Rosado David, José Mª Mateos Galván
P43 Granuloma annulare after therapy with canakinumab
Razvigor Darlenski
P44 Hypersensitivity eosinophilic myocarditis or acute coronary syndrome? Case report
Dario Gulin, Jozica Sikic, Jasna Cerkez Habek, Sandra Jerkovic Gulin, Edvard Galic
P45 Piperacillin-induced immune haemolytic anaemia: a severe and frequent complication of antibiotic treatment in patients with cystic fibrosis
Philip Specht, Doris Staab, Beate Mayer, Jobst Roehmel
P46 Progesterone triggered pemphigus foliaceus: case report
Sandra Jerkovic Gulin, Caius Solovan, Anca Chiriac
P47 Ramipril: triggered generalized pustular psoriasis
Paola Djurinec, Kresimir Kostovic, Mirna Bradamante, Sandra Jerkovic Gulin, Romana Ceovic
Poster Walk 6: NSAIDs (P48–P56)
P48 Aspirin desensitization in cardiovascular disease—Portuguese experience
Jose Pedro Almeida, Joana Caiado, Elisa Pedro, Pedro Canas Da Silva, Manuel Pereira Barbosa
P49 Asthma and/or rhinitis to NSAIDs with good tolerance to ASA
Gador Bogas, Natalia Blanca-López, Diana Pérez-Alzate, Inmaculada Doña, José Augusto Agúndez, Elena García-Martín, José Antonio Cornejo-García, Cristobalina Mayorga, María José Torres, Gabriela Canto, Miguel Blanca
P50 Clinical characteristics of 196 patients with non-steroidal anti-inflammatory drug (NSAIDs) hypersensitivity
Sengül Aksakal, Aytül Zerrin Sin, Zeynep Peker Koç, Fatma Düsünür Günsen, Ömür Ardeniz, Emine Nihal Mete Gökmen, Okan Gülbahar, Ali Kokuludag
P51 Development of immediate hypersensitivity to several NSAIDs maintaining good tolerance to ASA
Natalia Pérez-Sánchez, Natalia Blanca-López, Diana Pérez-Alzate, Gador Bogas, Inmaculada Doña, María Salas, María José Torres, Miguel Blanca, Gabriela Canto
P52 Diagnosis of hypersensitivity reactions to paracetamol in a large series of cases
Inmaculada Doña, Maria Salas, Francisca Gomez, Natalia Blanca-Lopez, Diana Perez-Alzate, Gador Bogas, Esther Barrionuevo, Maria Jose Torres, Inmaculada Andreu, Miguel Ángel Miranda, Gabriela Canto, Miguel Blanca
P53 Hypersensitivity to paracetamol according to the new classification of hypersensitivity to NSAIDs
Gabija Didžiokaite, Olesia Gaidej, Simona Kašinskaite, Violeta Kvedariene
P54 Ibuprofen and other aryl propionic derivates can induce immediate selective hypersensitivity responses
Diana Perez-Alzate, Natalia Blanca-López, Maria Isabel Garcimartin, Inmaculada Doña, Maria Luisa Somoza, Cristobalina Mayorga, Maria Jose Torres, Gador Bojas, Jose Antonio Cornejo-Garcia, Maria Gabriela Canto, Miguel Blanca
P55 Subjects developing immediate responses to several NSAIDs can be selective with good tolerance to ASA
Natalia Blanca-Lopez, Diana Pérez-Alzate, Francisco Javier Ruano Perez, Inmaculada Doña, Maria Luisa Somoza, Inmaculada Andreu, Miguel Angel Miranda, Cristobalina Mayorga, Maria Jose Torres, Jose Antonio Cornejo-Garcia, Miguel Blanca, Maria Gabriela Canto
P56 Utility of low-dose oral aspirin challenges for diagnosis of aspirin exacerbated respiratory disease
Elina Jerschow, Teresa Pelletier, Zhen Ren, Golda Hudes, Marek Sanak, Esperanza Morales, Victor Schuster, Simon D. Spivack, David Rosenstreich
Poster Walk 7: NSAID 2 (P57–P65)
P57 Alternate regulation of cyclooxygenase-2 (COX-2) MRNA expression may predispose patients to aspirin-induced exacerbations
Renato Erzen, Mira Silar, Nissera Bajrovic, Matija Rijavec, Mihaela Zidarn, Peter Korosec
P58 Anaphylaxis to diclofenac: what about the underlying mechanism?
Leonor Carneiro-Leão, Fabrícia Carolino, Luís Amaral, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas
P59 COX-2 inhibitors: are they always a safe alternative in hypersensitivity to nonsteroidal anti-inflammatory drugs?
Luis Amaral, Fabricia Carolino, Eunice Castro, Josefina Cernadas
P60 Management of patients with history of NSAIDs reactions prior to coronary angioplasty
Mona Al-Ahmad, Tito Rodriguez
P61 Oral drug challenge with non-steroidal anti-inflammatory drug under spirometric control: clinical series of 110 patients
João Pedro Azevedo, Emília Faria, Beatriz Tavares, Frederico Regateiro, Ana Todo-Bom
P62 Prevalence and incidence of analgesic hypersensitivity reactions in Colombia
Pablo Andrés Miranda, Bautista De La Cruz Hoyos
P63 Recent endoscopic sinus surgery lessens reactions during aspirin challenge in patients with aspirin exacerbated respiratory disease
Teresa Pelletier, Waleed Abuzeid, Nadeem Akbar, Marc Gibber, Marvin Fried, Weiguo Han, Taha Keskin, Robert Tamayev, Golda Hudes, Simon D. Spivack, David Rosenstreich, Elina Jerschow
P64 Safe use of imidazole salycilate in a case of multiple NSAIDs induced urticaria-angioedema
Elisa Boni, Marina Russello, Marina Mauro
P65 Selective hypersensitivity reactions to ibuprofen—seven years experience
Marta Ferreira Neto
Poster Walk 8: Epidemiological methods (P66–P72)
P66 Allopurinol hypersensitivity: a 7-year review
Lise Brosseron, Daniela Malheiro, Susana Cadinha, Patrícia Barreira, J. P. Moreira Da Silva
P67 Antibiotic allergy labelling is associated with increased hospital readmission rates in Australia
Brittany Knezevic, Dustin Sprigg, Michelle Trevenen, Jason Seet, Jason Trubiano, William Smith, Yogesh Jeelall, Sandra Vale, Richard Loh, Andrew Mclean-Tooke, Michaela Lucas
P68 Experts’ opinions on severe cutaneous adverse drug reactions-report of a survey from the 9th international congress on cutaneous adverse drug reactions 2015
Roni P. Dodiuk-Gad, Cristina Olteanu, Wen-Hung Chung, Neil H. Shear
P69 HLA-A*31-positive AGEP with carbamazepine use and other severe cutaneous adverse drug reactions (SCARs) detected by electronic medical records screening
Sabine Müller, Ursula Amstutz, Lukas Jörg, Nikhil Yawalkar, Stephan Krähenbühl
P70 Patients with suspected drug allergy: a specific psychological profile?
Eunice Dias-Castro, Ana Leblanc, Laura Ribeiro, Josefina R. Cernadas
P71 Use of an electronic device and a computerized mathematic algorithm to detect the allergic drug reactions through the analysis of heart rate variability
Arantza Vega, Raquel Gutierrez Rivas, Ana Alonso, Juan Maria Beitia, Belén Mateo, Remedios Cárdenas, Juan Jesus Garcia-Dominguez
P72 Variation in ERAP influences risk for HLA-B*57:01 positive abacavir hypersensitivity
Rebecca Pavlos, Kaija Strautins, Ian James, Simon Mallal, Alec Redwood, Elizabeth Phillips
Poster Walk 9: DRESS/AGEP (P73–P81)
P73 A clinical case of DRESS syndrome in a child after administration of amoxicillin-clavulanic acid
Rita Aguiar, Anabela Lopes, Ana Neves, Maria Do Céu Machado, M. A. Pereira-Barbosa
P74 Acute generalized exanthematous pustulosis (AGEP) induced by mesalazine, reliable and oftenly used drug to treat inflammatory bowel disease
Ceyda Tunakan Dalgiç, Emine Nihal Mete Gökmen, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Ali Kokuludag, Aytül Zerrin Sin
P75 Changes of blood plasmacytoid dendritic cells, myeloid dendritic cells, and basophils during the acute stage of drug reaction with eosinophilia and systemic symptoms (DRESS) and other drug eruptions
Shao-Hsuan Hsu, Yung-Tsu Cho, Che-Wen Yang, Kai-Lung Chen, Chia-Yu Chu
P76 Characterization of isoniazid/rifampicin-specific t-cell responses in patients with DRESS syndrome
Young-Min Ye, Gyu-Young Hur, Hae-Sim Park, Seung-Hyun Kim
P77 DRESS syndrome secondary to sulfasalazine with delayed TEN: a case presentation
Syed Ali, Michaela Lucas, Peter N. Hollingsworth, Andrew P. C. Mclean-Tooke
P78 Drug rash with eosinophilia and systemic symptoms (DRESS) features according to the culprit drug
Zohra Chadly, Nadia Ben Fredj, Karim Aouam, Haifa Ben Romdhane, Naceur A. Boughattas, Amel Chaabane
P79 Drug reaction with eosinophilia and systemic symptoms induced by allopurinol: not always easy to diagnose
Marina Lluncor Salazar, Beatriz Pola, Ana Fiandor, Teresa Bellón, Elena Ramírez, Javier Domínguez Ortega, Santiago Quirce, Rosario Cabañas
P80 Drug reaction with eosinophilia and systemic symptoms syndrome induced by two drugs simultaneously: a case report
Krasimira Baynova, Marina Labella, Manuel Prados
P81 The drug reaction with eosinophilia and systemic symptoms (DRESS) induced by the second-line antituberculosis drugs and Epstein–Barr virus infection
Agne Ramonaite, Ieva Bajoriuniene, Brigita Sitkauskiene, Raimundas Sakalauskas
Poster Walk 10: Miscellaneous drug hypersensitivity (P82–P91)
P82 A case of cycloserine-induced lichenoid drug eruption confirmed with a lymphocatye transformation test
Jae-Woo Kwon, Shinyoung Park
P83 Allergic reaction to topical eye drops: 5 years’ retrospective study in a drug allergy unit
Diana Silva, Leonor Carneiro Leão, Fabricia Carolino, Eunice Castro, Josefina Cernadas
P84 Allergy to heparins
Diana Perez-Alzate, Natalia Blanca-López, Maria Luisa Somoza Alvarez, Maria Garcimartin, Maria Vazquez De La Torre, Francisco Javier Ruano Pérez, Elisa Haroun, Gabriela Canto Diez
P85 Allopurinol-induced adverse drug reactions
Katinka Ónodi-Nagy, Ágnes Kinyó, Lajos Kemény, Zsuzsanna Bata-Csörgo
P86 Analysis of a population with immediate hypersensitivity to corticosteroids: an 11 year review
Joana Sofia Pita, Emília Faria, Rosa Anita Fernandes, Ana Moura, Nuno Sousa, Carmelita Ribeiro, Carlos Loureiro, Ana Todo Bom
P87 Anaphylaxis against mivacurium in a 12-months old boy at first-time exposure
Wolfgang Pfützner
P88 Antihistamine-exacerbated chronic spontaneous urticaria: a paradox?
Nadine Marrouche, Clive Grattan
P89 Anti-osteoporotic agents-induced cutaneous adverse drug reactions in Asians
Yu-En Chen, Chun-Bing Chen, Wen-Hung Chung, Yu-Ping Hsiao, Chia-Yu Chu
P90 Diagnosis of allergic reactions to eye drops
Maria Vazquez De La Torre, Natalia Blanca-Lopez, Diana Perez-Alzate, Maria Isabel Garcimartin, Francisco Javier Ruano, Maria Luisa Somoza, Elisa Haroun, Gabriela Canto
P91 Diagnostic approach in suspected hypersensitivity reactions to corticosteroids
Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas
doi:10.1186/s13601-016-0121-z
PMCID: PMC5009634
5.  HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4+ T Cell Responses 
Journal of Virology  2016;90(5):2208-2220.
ABSTRACT
Antigen-specific CD4+ T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+ T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+ T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+ T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+ T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+ T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+ T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+ T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+ T cells and, to a lesser extent, gp41-specific CD4+ T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies.
IMPORTANCE One of the earliest discoveries related to CD4+ T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+ T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+ T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+ T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+ T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+ T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection.
doi:10.1128/JVI.02278-15
PMCID: PMC4810720  PMID: 26656715
6.  Identification of Siglec-1 null individuals infected with HIV-1 
Nature Communications  2016;7:12412.
Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals.
Binding of virus, HIV-1, to cellular protein Siglec-1 is important for infection of immune cells. Here the authors show that a natural mutation leading to production of truncated Siglec-1 reduces HIV binding and infectivity transfer in vitro, but does not substantially affect infection or AIDS outcome in patients.
doi:10.1038/ncomms12412
PMCID: PMC4987525  PMID: 27510803
8.  Epigenetic regulation of differential HLA-A allelic expression levels 
Human Molecular Genetics  2015;24(15):4268-4275.
MHC class I expression levels influence the strength of immune responses and represent another variable in determining outcome to disease beyond peptide binding alone. Identification of the HLA loci that vary in allelic expression levels and delineating the mechanism responsible for expression variation may provide the opportunity to modify their expression therapeutically. We have examined the expression levels of allelic lineages at the HLA-A locus in a sample of 216 European Americans using a real-time polymerase chain reaction assay, which amplifies all HLA-A lineages specifically with equal efficiency, and observed a gradient of expression that associates with HLA-A allelic lineage (R = 0.6, P = 5 × 10−25). DNA methylation of the HLA-A gene appears to contribute to the variation in HLA-A mRNA expression levels, as a significant inverse correlation was observed between HLA-A mRNA expression levels in untreated cells and the degree to which expression is increased after treatment of the cells with a DNA methyltransferase inhibitor (R = 0.6, P = 2.8 × 10−6). Further, deep-sequencing and immunoprecipitation assays revealed allelic lineage-specific methylation patterns within the HLA-A promoter region where increased DNA methylation levels correlated significantly with reduced HLA-A expression levels (R = 0.89, P = 3.7 × 10−9). These data demonstrate HLA-A allelic lineage-specific variation in expression levels, and DNA methylation as a likely factor in contributing to this variation.
doi:10.1093/hmg/ddv158
PMCID: PMC4492392  PMID: 25935001
9.  Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic 
Journal of Virology  2016;90(3):1244-1258.
ABSTRACT
Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era.
IMPORTANCE HLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many—though not all—HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era.
doi:10.1128/JVI.02353-15
PMCID: PMC4719594  PMID: 26559841
10.  Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo 
European journal of immunology  2015;45(7):2052-2060.
Although HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidences for in vivo relevance of this interaction is still missing. To explore the functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, known to be negatively associated with activating KIR genes. The frequency of KIR3DL2*001 was increased in patients (OR=2.04, p=0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or A11 (OR=3.76, p=0.013), providing the first evidence that HLA-A3 and A11 may interact with KIR3DL2 in vivo. The non-synonymous single nucleotide polymorphism 1190T (rs3745902) was associated with protection (OR=0.52, p=0.018). This SNP results in a threonine to methionine substitution. Individuals who have methionine in this position exhibit a lower percentage of KIR3DL2 positive cells and also lower intensity of KIR3DL2 on expressing cells; additionally, we show that the expression of KIR3DL2 is independent of other killer cell immunoglobulin-like receptors. Pemphigus foliaceus is a very unique complex disease strongly associated with immune-related genes. It is the only autoimmune disease known to be endemic, showing a strong correlation with environmental factors. Our data demonstrate that this relatively unknown autoimmune disease may facilitate understanding of the molecular mechanisms of KIR3DL2 ligand recognition.
doi:10.1002/eji.201445324
PMCID: PMC4530613  PMID: 25867094
KIR; autoimmunity; allele polymorphism; ligands; expression; pemphigus foliaceus; MHC; natural killer cells
11.  HIV-1 Vpu Mediates HLA-C Downregulation 
Cell host & microbe  2016;19(5):686-695.
SUMMARY
Many pathogens evade cytotoxic T lymphocytes (CTLs) by downregulating HLA molecules on infected cells, but the loss of HLA can trigger NK cell-mediated lysis. HIV-1 is thought to subvert CTLs while preserving NK cell inhibition by Nef-mediated downregulation of HLA-A and -B but not HLA-C molecules. We find that HLA-C is downregulated by most primary HIV-1 clones, including transmitted founder viruses, in contrast to the laboratory-adapted NL4-3 virus. HLA-C reduction is mediated by viral Vpu and reduces the ability of HLA-C restricted CTLs to suppress viral replication in CD4+ cells in vitro. HLA-A/B are unaffected by Vpu, and primary HIV-1 clones vary in their ability to downregulate HLA-C, possibly in response to whether CTLs or NK cells dominate immune pressure through HLA-C. HIV-2 also suppresses HLA-C expression through distinct mechanisms, underscoring the immune pressure HLA-C exerts on HIV. This viral immune evasion casts new light on the roles of CTLs and NK cells in immune responses against HIV.
Graphical Abstract
doi:10.1016/j.chom.2016.04.005
PMCID: PMC4904791  PMID: 27173934
12.  Relative expression levels of the HLA class-I proteins in normal and HIV-infected cells 1 
The expression level of human leukocyte antigens (HLA) is known to influence pathological outcomes: pathogens downregulate HLA to evade host immune responses, host inflammatory reactions upregulate HLA, and differences between people in steady-state expression levels of HLA associate with disease susceptibility. Yet precise quantification of relative expression levels of the various HLA loci is difficult due to the tremendous polymorphism of HLA. We report relative expression levels of HLA-A, HLA-B, HLA-C and HLA-E proteins for the specific haplotype A*02:01, B*44:02, C*05:01, characterized using two independent methods based on flow cytometry and mass spectrometry. Peripheral blood lymphocytes from normal donors showed that HLA-A and HLA-B proteins are expressed at similar levels, which are 13-18 times higher than HLA-C by flow cytometry and 4-5 times higher than HLA-C by mass spectrometry, differences that may reflect variation in the conformation or location of proteins detected. HLA-E was detected at a level 25 times lower than that of HLA-C by mass spectrometry. Primary CD4+ T cells infected with HIV in vitro were also studied since HIV downregulates selective HLA types. HLA-A and -B were reduced on HIV-infected cells by a magnitude that varied between cells in an infected culture. Averaging all infected cells from an individual showed HLA-A to be 1-3 and HLA-B to be 2-5 times higher than HLA-C for different individuals by flow cytometry. These results quantify substantial differences in expression levels of the proteins from different HLA loci, which are very likely physiologically significant on both uninfected and HIV-infected cells.
doi:10.4049/jimmunol.1403234
PMCID: PMC4390493  PMID: 25754738
13.  Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline during Latency-Reversing Treatment with Panobinostat 
Journal of Virology  2015;89(20):10176-10189.
ABSTRACT
The pharmaceutical reactivation of dormant HIV-1 proviruses by histone deacetylase inhibitors (HDACi) represents a possible strategy to reduce the reservoir of HIV-1-infected cells in individuals treated with suppressive combination antiretroviral therapy (cART). However, the effects of such latency-reversing agents on the viral reservoir size are likely to be influenced by host immune responses. Here, we analyzed the immune factors associated with changes in proviral HIV-1 DNA levels during treatment with the potent HDACi panobinostat in a human clinical trial involving 15 cART-treated HIV-1-infected patients. We observed that the magnitude, breadth, and cytokine secretion profile of HIV-1-specific CD8 T cell responses were unrelated to changes in HIV-1 DNA levels in CD4 T cells during panobinostat treatment. In contrast, the proportions of CD3− CD56+ total NK cells and CD16+ CD56dim NK cells were inversely correlated with HIV-1 DNA levels throughout the study, and changes in HIV-1 DNA levels during panobinostat treatment were negatively associated with the corresponding changes in CD69+ NK cells. Decreasing levels of HIV-1 DNA during latency-reversing treatment were also related to the proportions of plasmacytoid dendritic cells, to distinct expression patterns of interferon-stimulated genes, and to the expression of the IL28B CC genotype. Together, these data suggest that innate immune activity can critically modulate the effects of latency-reversing agents on the viral reservoir and may represent a target for future immunotherapeutic interventions in HIV-1 eradication studies.
IMPORTANCE Currently available antiretroviral drugs are highly effective in suppressing HIV-1 replication, but the virus persists, despite treatment, in a latent form that does not actively express HIV-1 gene products. One approach to eliminate these cells, colloquially termed the “shock-and-kill” strategy, focuses on the use of latency-reversing agents that induce active viral gene expression in latently infected cells, followed by immune-mediated killing. Panobinostat, a histone deacetylase inhibitor, demonstrated potent activities in reversing HIV-1 latency in a recent pilot clinical trial and reduced HIV-1 DNA levels in a subset of patients. Interestingly, we found that innate immune factors, such as natural killer cells, plasmacytoid dendritic cells, and the expression patterns of interferon-stimulated genes, were most closely linked to a decline in the HIV-1 DNA level during treatment with panobinostat. These data suggest that innate immune activity may play an important role in reducing the residual reservoir of HIV-1-infected cells.
doi:10.1128/JVI.01484-15
PMCID: PMC4580197  PMID: 26223643
14.  Proceedings of the 7th Biannual International Symposium on Nasopharyngeal Carcinoma 2015 
Tan, IB | Chang, Ellen T. | Chen, Chien-Jen | Hsu, Wan-Lun | Chien, Yin-Chu | Hildesheim, Allan | McKay, James D. | Gaborieau, Valerie | Kaderi, Mohamed Arifin Bin | Purnomosari, Dewajani | Voegele, Catherine | LeCalvez-Kelm, Florence | Byrnes, Graham | Brennan, Paul | Devi, Beena | Li, L. | Zhang, Y. | Fan, Y. | Sun, K. | Du, Z. | Sun, H. | Chan, A. T. | Tsao, S. W. | Zeng, Y. X. | Tao, Q. | Busson, Pierre | Lhuillier, Claire | Morales, Olivier | Mrizak, Dhafer | Gelin, Aurore | Kapetanakis, Nikiforos | Delhem, Nadira | Mansouri, Sheila | Cao, Jennifer | Vaidya, Anup | Frappier, Lori | Wai, Lo Kwok | Chen, Sui-Hong | Du, Jin-lin | Ji, Ming-Fang | Huang, Qi-Hong | Liu, Qing | Cao, Su-Mei | Doolan, Denise L. | Coghill, Anna | Mulvenna, Jason | Proietti, Carla | Lekieffre, Lea | Bethony, Jeffrey | Hildesheim, and Allan | Fles, Renske | Indrasari, Sagung Rai | Herdini, Camelia | Martini, Santi | Isfandiari, Atoillah | Rhomdoni, Achmad | Adham, Marlinda | Mayangsari, Ika | van Werkhoven, Erik | Wildeman, Maarten | Hariwiyanto, Bambang | Hermani, Bambang | Kentjono, Widodo Ario | Haryana, Sofia Mubarika | Schmidt, Marjanka | Tan, IB | O’Sullivan, Brian | Ozyar, Enis | Lee, Anne W. M. | Zeng, Mu-Sheng | Gao, Xiaojiang | Tang, Minzhong | Martin, Pat | Zeng, Yi | Carrington, Mary | Coghill, Anna E. | Bu, Wei | Nguyen, Hanh | Hsu, Wan-Lun | Yu, Kelly J. | Lou, Pei-Jen | Wang, Cheng-Ping | Chen, Chien-Jen | Hildesheim, Allan | Cohen, Jeffrey I. | King, Ann D. | Chien, Yin-Chu | Hsu, Wan-Lun | Yu, Kelly J. | Chen, Tseng-Cheng | Lin, Ching-Yuan | Tsou, Yung-An | Leu, Yi-Shing | Laio, Li-Jen | Chang, Yen-Liang | Wang, Cheng-Ping | Hua, Chun-Hun | Wu, Ming-Shiang | Hsiao, Chu-Hsing Kate | Lee, Jehn-Chuan | Tsai, Ming-Hsui | Cheng, Skye Hung-Chun | Lou, Pei-Jen | Hildesheim, Allan | Chen, Chien-Jen | Hsu, Wan-Lun | Yu, Kelly J. | Chien, Yin-Chu | Chen, Tseng-Cheng | Lin, Ching-Yuan | Tsou, Yung-An | Leu, Yi-Shing | Liao, Li-Jen | Chang, Yen-Liang | Yang, Tsung-Lin | Hua, Chun-Hun | Wu, Ming-Shiang | Hsiao, Chu-Hsing Kate | Lee, Jehn-Chuan | Tsai, Ming-Hsui | Cheng, Skye Hung-Chun | Ko, Jenq-Yuh | Hildesheim, Allan | Chen, Chien-Jen | Ko, Josephine Mun Yee | Dai, Wei | Kwong, Dora | Ng, Wai Tong | Lee, Anne | Ngan, Roger Kai Cheong | Yau, Chun Chung | Tung, Stewart | Lung, Maria Li | Ji, Mingfang | Sheng, Wei | Ng, Mun Hon | Cheng, Weimin | Yu, Xia | Wu, Biaohua | Wei, Kuangrong | Zhan, Jun | Zeng, Yi Xin | Cao, Su Mei | Xia, Ningshao | Yuan, Yong | Cui, Qian | Xu, Miao | Bei, Jin-Xin | Zeng, Yi-Xin | Şahin, B | Dizman, A | Esassolak, M | İkizler, A Saran | Yıldırım, HC | Çaloğlu, M | Atalar, B | Akman, F | Demiroz, C | Atasoy, BM | Canyilmaz, E | Igdem, S | Ugurluer, G | Kütük, T | Akmansoy, M | Ozyar, E | Sommat, Kiattisa | Wang, Fu Qiang | Kwok, Li-Lian | Tan, Terence | Fong, Kam Weng | Soong, Yoke Lim | Cheah, Shie Lee | Wee, Joseph | Casanova, M | Özyar, E | Patte, C | Orbach, D | Ferrari, A | Cristine, VF | Errihani, H | Pan, J | Zhang, L | Liji, S | Grzegorzewski, K | Gore, L | Varan, A | Hutajulu, Susanna Hilda | Khuzairi, Guntara | Herdini, Camelia | Kusumo, Henry | Hardianti, Mardiah Suci | Taroeno-Hariadi, Kartika Widayati | Purwanto, Ibnu | Kurnianda, Johan | Messick, Troy E. | Malecka, Kimberly | Tolvinski, Lois | Soldan, Samantha | Deakyne, Julianna | Song, Hui | van den Heuvel, Antonio | Gu, Baiwei | Cassel, Joel | McDonnell, Mark | Smith, Garry R. | Velvadapu, Venkata | Bian, Haiyan | Zhang, Yan | Carlsen, Marianne | Chen, Shuai | Donald, Alastair | Lemmen, Christian | Reitz, Allen B. | Lieberman, Paul M. | Chan, King Chi | Chan, Lai Sheung | Lo, Kwok Wai | Yip, Timothy Tak Chun | Ngan, Roger Kai Cheong | Kahn, Michael | Lung, Maria Li | Mak, Nai Ki | Liu, Fei-Fei | Khaali, Wafa | Thariat, Juliette | Fantin, Laurence | Spirito, Flavia | Khyatti, Meriem | Driss, El Khalil Ben | Olivero, Sylvain | Maryanski, Janet | Doglio, Alain | Xia, Mengxue | Xia, Yunfei | Chang, Hui | Shaw, Rachel | Rahaju, Pudji | Hardianti, Mardiah Suci | Wisesa, Sindhu | Taroeno-Harijadi, Kartika Widayati | Purwanto, Ibnu | Hariwiyanto, Bambang | Dhamiyati, Wigati | Kurnianda, Johan | Tan, Sang-Nee | Sim, Sai-Peng | Yusuf, Muhtarum | Romdhoni, Ahmad C. | K, Widodo Ario | Rantam, Fedik Abdul | Sugiyanto | Aryati, Lina | Adi-Kusumo, Fajar | Hardianti, Mardiah Suci | Bintoro, SY | Oktriani, R. | Herawati, C. | Surono, A. | Haryana, Sofia M. | Zhong, L. | Li, L. | Ma, B. B. | Chan, A. T. | Tao, Q. | Kalra, M. | Ngo, M. | Perna, S. | Leen, A. | Lapteva, N. | Rooney, C. M. | Gottschalk, S. | Mustikaningtyas, Elida | Herawati, Sri | Romdhoni, Achmad C. | Ji, Mingfang | Xu, Yarui | Cheng, Weimin | Ge, Shengxiang | Li, Fugui | Ng, M. H. | Tan, Louise SY | Wong, Benjamin | Lim, C. M. | Romdhoni, Achmad C. | Rantam, Fedik A. | Kentjono, Widodo Ario | Madani, Deasy Z. | Akbar, Nur | Permana, Agung Dinasti | Herdini, Camelia | Indrasari, Sagung Rai | Fachiroh, Jajah | Hartati, Dwi | Rahayudjati, T. Baning | Darwis, Iswandi | Hutajulu, Susanna Hilda | Hariwiyanto, Bambang | Dhamiyati, Wigati | Purwanto, Ibnu | Taroeno-Hariadi, Kartika Widayati | Kurnianda, Johan | Wisesa, Sindhu | Hardianti, Mardiah Suci | Hutajulu, Susanna Hilda | Taroeno-Harijadi, Kartika Widayati | Purwanto, Ibnu | Herdini, Camelia | Dhamiyati, Wigati | Kurnianda, Johan | Anwar, Khoirul | Hutajulu, Susanna Hilda | Indrasari, Sagung Rai | Dwidanarti, Sri Retna | Purwanto, Ibnu | Taroeno-Hariadi, Kartika Widayati | Kurnianda, Johan | Pramana, Dominicus Wendhy | Hutajulu, Susanna Hilda | Hariwiyanto, Bambang | Dhamiyati, Wigati | Purwanto, Ibnu | Taroeno-Hariadi, Kartika Widayati | Kurnianda, Johan | Safitri, Diah Ari | Hutajulu, Susanna Hilda | Herdini, Camelia | Danarti, Sri Retna Dwi | Purwanto, Ibnu | Taroeno-Hariadi, Kartika Widayati | Kurnianda, Johan | Taroeno, Suryo A | Wisesa, Sindhu | Taroeno-Hariadi, Kartika Widayati | Purwanto, Ibnu | Hariwiyanto, Bambang | Dhamiyati, Wigati | Kurnianda, Johan | Wijaya, I. | Oehadian, A. | Prasetya, D. | Hsu, Wan-Lun | Chien, Yin-Chu | Yu, Kelly J | Wang, Cheng-Ping | Lin, Ching-Yuan | Tsou, Yung-An | Leu, Yi-Shing | Liao, Li-Jen | Chang, Yen-Liang | Ko, Jenq-Yuh | Hua, Chun-Hun | Wu, Ming-Shiang | Hsiao, Chu-Hsing Kate | Lee, Jehn-Chuan | Tsai, Ming-Hsui | Cheng, Skye Hung-Chun | Lou, Pei-Jen | Hildesheim, Allan | Chen, Chien-Jen | Rahman, Sukri | Budiman, Bestari J. | Novialdi | Rahmadona | Lestari, Dewi Yuri | Yin, C. | Foussadier, A. | Blein, E. | Chen, C. | Ammour, N. Bournet | Khiatti, M. | Cao, S. | Marzaini, Dewi Syafriyetti Soeis | Hartati, Dwi | Rahayujati, Baning | Herdini, Camelia | Fachiroh, Jajah | Gunawan, L. | Mubarika Haryana, S. | Surono, A. | Herawati, C. | Hartono, Michael | Fachiroh, Jajah | Intansari, Umi | Paramita, Dewi Kartikawati | Akbar, Akmal | Fachiroh, Jajah | Paramita, Dewi Kartikawati | Hermawan, Benny | Rahayudjati, T. Baning | Paramita, Dewi K. | Fachiroh, Jajah | Argy, Gabriella | Fachiroh, Jajah | Paramita, Dewi Kartikawati | Hutajulu, Susanna Hilda | Sihotang, Theodora Caroline | Fachiroh, Jajah | Intansari, Umi | Paramita, Dewi Kartikawati | Wahyono, Daniel Joko | Soeharso, Purnomo | Suryandari, Dwi Anita | Lisnawati | Musa, Zanil | Hermani, Bambang | Daker, Maelinda | Tzen, Yeo Jiun | Bakar, Norhasimah | Rahman, Asma’ Saiyidatina Aishah Abdul | Ahmad, Munirah | Chia, Yeo Tiong | Beng, Alan Khoo Soo | Sasikirana, Widyandani | Wardana, Tirta | Radifar, Muhammad | Herawati, Cita | Surono, Agus | Haryana, Sofia Mubarika
BMC Proceedings  2016;10(Suppl 1):1.
Table of contents
A1 Hope and despair in the current treatment of nasopharyngeal cancer
IB Tan
I1 NPC international incidence and risk factors
Ellen T Chang
I2 Familial nasopharyngeal carcinoma and the use of biomarkers
Chien-Jen Chen, Wan-Lun Hsu, Yin-Chu Chien
I3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findings
Allan Hildesheim
I5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast Asia
James D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena Devi
I6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylation
Li L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao Q
I7 Tumor exosomes and translational research in NPC
Pierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira Delhem
I8 Host manipulations of the Epstein-Barr virus EBNA1 protein
Sheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori Frappier
I9 Somatic genetic changes in EBV-associated nasopharyngeal carcinoma
Lo Kwok Wai
I10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern China
Sui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei Cao
I11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disorders
Denise L. Doolan, Anna Coghill, Jason Mulvenna, Carla Proietti, Lea Lekieffre, Jeffrey Bethony, and Allan Hildesheim
I12 The nasopharyngeal carcinoma awareness program in Indonesia
Renske Fles, Sagung Rai Indrasari, Camelia Herdini, Santi Martini, Atoillah Isfandiari, Achmad Rhomdoni, Marlinda Adham, Ika Mayangsari, Erik van Werkhoven, Maarten Wildeman, Bambang Hariwiyanto, Bambang Hermani, Widodo Ario Kentjono, Sofia Mubarika Haryana, Marjanka Schmidt, IB Tan
I13 Current advances and future direction in nasopharyngeal cancer management
Brian O’Sullivan
I14 Management of juvenile nasopharyngeal cancer
Enis Ozyar
I15 Global pattern of nasopharyngeal cancer: correlation of outcome with access to radiotherapy
Anne WM Lee
I16 The predictive/prognostic biomarker for nasopharyngeal carcinoma
Mu-Sheng Zeng
I17 Effect of HLA and KIR polymorphism on NPC risk
Xiaojiang Gao, Minzhong Tang, Pat Martin, Yi Zeng, Mary Carrington
I18 Exploring the Association between Potentially Neutralizing Antibodies against EBV Infection and Nasopharyngeal Carcinoma
Anna E Coghill, Wei Bu, Hanh Nguyen, Wan-Lun Hsu, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Chien-Jen Chen, Allan Hildesheim, Jeffrey I Cohen
I19 Advances in MR imaging in NPC
Ann D King
O1 Epstein-Barr virus seromarkers and risk of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan
Yin-Chu Chien, Wan-Lun Hsu, Kelly J Yu, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Laio, Yen-Liang Chang, Cheng-Ping Wang, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen
O2 Familial tendency and environmental co-factors of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan
Wan-Lun Hsu, Kelly J Yu, Yin-Chu Chien, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang, Tsung-Lin Yang, Chun-Hun Hua, Ming-ShiangWu, Chu-Hsing Kate Hsiao, Jehn-ChuanLee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Jenq-Yuh Ko, Allan Hildesheim, Chien-Jen Chen
O3 The genetic susceptibility and prognostic role of TERT-CLPTM1L and genes in DNA damage pathways in NPC
Josephine Mun Yee Ko, Wei Dai, Dora Kwong, Wai Tong Ng, Anne Lee, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Maria Li Lung
O4 Long term effects of NPC screening
Mingfang Ji, Wei Sheng, Mun Hon Ng, Weimin Cheng, Xia Yu, Biaohua Wu, Kuangrong Wei, Jun Zhan, Yi Xin Zeng, Su Mei Cao, Ningshao Xia, Yong Yuan
O5 Risk prediction of nasopharyngeal carcinoma by detecting host genetic and Epstein-Barr virus variation in saliva
Qian Cui, Miao Xu, Jin-Xin Bei, Yi-Xin Zeng
O6 Patterns of care study in Turkish nasopharyngeal cancer patients (NAZOTURK): A Turkish Radiation Oncology Association Head and Neck Cancer Working Group Study
B Şahin, A Dizman, M Esassolak, A Saran İkizler, HC Yıldırım, M Çaloğlu, B Atalar, F Akman, C Demiroz, BM Atasoy, E Canyilmaz, S Igdem, G Ugurluer, T Kütük, M Akmansoy, E Ozyar
O7 Long term outcome of intensity modulated radiotherapy in nasopharyngeal carcinoma in National Cancer Centre Singapore
Kiattisa Sommat, Fu Qiang Wang, Li-Lian Kwok, Terence Tan, Kam Weng Fong, Yoke Lim Soong, Shie Lee Cheah, Joseph Wee
O8 International phase II randomized study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents
M Casanova, E Özyar, C Patte, D Orbach, A Ferrari, VF Cristine, H Errihani, J Pan, L Zhang, S Liji, K Grzegorzewski, L Gore, A Varan
O9 Prognostic impact of metastatic status in patients with nasopharyngeal carcinoma
Susanna Hilda Hutajulu, Guntara Khuzairi, Camelia Herdini, Henry Kusumo, Mardiah Suci Hardianti, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Johan Kurnianda
O10 Development of small molecule inhibitors of latent Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma
Troy E. Messick, Kimberly Malecka, Lois Tolvinski, Samantha Soldan, Julianna Deakyne, Hui Song, Antonio van den Heuvel, Baiwei Gu, Joel Cassel, Mark McDonnell, Garry R Smith, Venkata Velvadapu, Haiyan Bian, Yan Zhang, Marianne Carlsen, Shuai Chen, Alastair Donald, Christian Lemmen, Allen B Reitz, Paul M Lieberman
O11 Therapeutic targeting of cancer stem-like cells using a Wnt modulator, ICG-001, enhances the treatment outcome of EBV-positive nasopharyngeal carcinoma
King Chi Chan, Lai Sheung Chan, Kwok Wai Lo, Timothy Tak Chun Yip, Roger Kai Cheong Ngan, Michael Kahn, Maria Li Lung, Nai Ki Mak
O12 Role of micro-RNA in NPC biology
Fei-Fei Liu
O13 Expansion of EBNA1- and LMP2-specific effector T lymphocytes from patients with nasopharyngeal carcinoma without enhancement of regulatory T cells
Wafa Khaali; Juliette Thariat; Laurence Fantin; Flavia Spirito; Meriem Khyatti; El Khalil Ben Driss; Sylvain Olivero; Janet Maryanski; Alain Doglio
O14 The experience of patients’ life after amifostine radiotherapy treatment (ART) for nasopharyngeal carcinoma (NPC)
Mengxue Xia, Yunfei Xia, Hui Chang, Rachel Shaw
O15 Analysis of mitochondrial DNA mutation in latent membrane protein-1 positive nasopharyngeal carcinoma
Pudji Rahaju
O16 Factors influencing treatment adherence of nasopharyngeal cancer and the clinical outcomes: a hospital-based study
Mardiah Suci Hardianti, Sindhu Wisesa, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda
O17 Chromosomal breaks mediated by bile acid-induced apoptosis in nasopharyngeal epithelial cells: in relation to matrix association region/scaffold attachment region
Sang-Nee Tan, Sai-Peng Sim
O18 Expression of p53 (wild type) on nasopharyngeal carcinoma stem cell that resistant to radiotherapy
Muhtarum Yusuf, Ahmad C Romdhoni, Widodo Ario K, Fedik Abdul Rantam
O19 Mathematical model of nasopharyngeal carcinoma in cellular level
Sugiyanto, Lina Aryati, Fajar Adi-Kusumo, Mardiah Suci Hardianti
O20 Differential expression of microRNA-21 on nasopharyngeal carcinoma plasma patient
SY Bintoro, R Oktriani, C. Herawati, A Surono, Sofia M. Haryana
O21 Therapeutic targeting of an oncogenic fibroblast growth factor-FGF19, which promotes proliferation and induces EMT of carcinoma cells through activating ERK and AKT signaling
L. Zhong, L. Li, B. B. Ma, A. T. Chan, Q. Tao
O22 Resist nasopharyngeal carcinoma (NPC): next generation T cells for the adoptive immunotherapy of NPC
M. Kalra, M. Ngo, S. Perna, A. Leen, N. Lapteva, C. M. Rooney, S. Gottschalk
O23 The correlation of heat shock protein 70 expressions and staging of nasopharyngeal carcinoma
Elida Mustikaningtyas, Sri Herawati, Achmad C Romdhoni
O24 Epstein-Barr virus serological profiles of nasopharyngeal carcinoma - A tribute to Werner Henle
Mingfang Ji, YaruiXu, Weimin Cheng, ShengxiangGe, Fugui Li, M. H. Ng
O25 Targeting the apoptosis pathway using combination TLR3 agonist with anti-survivin molecule (YM-155) in nasopharyngeal carcinoma
Louise SY Tan, Benjamin Wong, CM Lim
O26 The resistance mechanism of nasopharyngeal cancer stem cells to cisplatin through expression of CD44, Hsp70, p53 (wild type), Oct-4, and ß-catenin encoded-genes
Achmad C Romdhoni, Fedik A. Rantam, Widodo Ario Kentjono
P1 Prevalence of nasopharyngeal carcinoma patients at Departement of Otorhinolaringology-Head and Neck Surgery, Dr. Hasan Sadikin general hospital, Bandung, Indonesia in 2010-2014
Deasy Z Madani, Nur Akbar, Agung Dinasti Permana
P2 Case report on pediatric nasopharyngeal carcinoma at Dr. Sardjito Hospital, Yogyakarta
Camelia Herdini, Sagung Rai Indrasari, Jajah Fachiroh, Dwi Hartati, T. Baning Rahayudjati
P3 Report on loco regionally advanced nasopharyngeal cancer patients treated with induction chemotherapy followed by concurrent chemo-radiation therapy
Iswandi Darwis, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda
P4 Sex and age differences in the survival of patients with nasopharyngeal carcinoma
Sindhu Wisesa, Mardiah Suci Hardianti, Susanna Hilda Hutajulu, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Camelia Herdini, Wigati Dhamiyati, Johan Kurnianda
P5 Impact of delayed diagnosis and delayed therapy in the treatment outcome of patients with nasopharyngeal carcinoma
Khoirul Anwar, Susanna Hilda Hutajulu, Sagung Rai Indrasari, Sri Retna Dwidanarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda
P6 Anaysis of pretreatment anemia in nasopharyngeal cancer patients undergoing neoadjuvant therapy
Dominicus Wendhy Pramana, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda
P7 Results of treatment with neoadjuvant cisplatin-5FU in locally advanced nasopharyngeal carcinoma: a local experience
Diah Ari Safitri, Susanna Hilda Hutajulu, Camelia Herdini, Sri Retna Dwi Danarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda
P8 Geriatrics with nasopharyngeal cancer
Suryo A Taroeno, Sindhu Wisesa, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda
P9 Correlation of lymphocyte to monocyte and neutrophil to lymphocyte ratio to the response of cisplatin chemoradiotheraphy in locally advance nasopharyngeal carcinoma
I. Wijaya, A. Oehadian, D. Prasetya
P10 Prediction of nasopharyngeal carcinoma risk by Epstein-Barr virus seromarkers and environmental co-factors: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan
Wan-Lun Hsu, Yin-Chu Chien, Kelly J Yu, Cheng-Ping Wang, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang191,192, Jenq-Yuh Ko, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen
P11 Non-viral risk factors for nasopharyngeal carcinoma in West Sumatra, Indonesia
Sukri Rahman, Bestari J. Budiman, Novialdi, Rahmadona, Dewi Yuri Lestari
P12 New prototype Vidas EBV IgA quick: performance on Chinese and Moroccan populations
C. Yin, A. Foussadier, E. Blein, C. Chen, N. Bournet Ammour, M. Khiatti, S. Cao
P13 The expression of EBV-LMP1 and VEGF as predictors and plasma EBV-DNA levels as early marker of distant metastasis after therapy in nasopharyngeal cancer
Dewi Syafriyetti Soeis Marzaini
P14 Characteristics and factors influencing subjects refusal for blood samples retrieval: lesson from NPC case control study in Yogyakarta – Indonesia
Dwi Hartati, Baning Rahayujati, Camelia Herdini, Jajah Fachiroh
P15 Expression of microRNA BART-7-3p and mRNA PTEN on blood plasma of patients with nasopharyngeal carcinoma
L. Gunawan, S. Mubarika Haryana, A. Surono, C. Herawati
P16 IgA response to native early antigen (IgA-EAext) of Epstein-Barr virus (EBV) in healthy population and nasopharyngeal carcinoma (NPC) patients: the potential for diagnosis and screening tools
Michael Hartono, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita
P17 IgA responses against Epstein-Barr Virus Early Antigen (EBV-EA) peptides as potential candidates of nasopharyngeal carcinoma detection marker
Akmal Akbar, Jajah Fachiroh, Dewi Kartikawati Paramita
P18 Association between smoking habit and IgA-EBV titer among healthy individuals in Yogyakarta, Indonesia
Benny Hermawan, T Baning Rahayudjati, Dewi K Paramita, Jajah Fachiroh
P19 Epstein-Barr virus IgA titer comparison of healthy non-family individuals and healthy first degree family of NPV patients
Gabriella Argy, Jajah Fachiroh, Dewi Kartikawati Paramita, Susanna Hilda Hutajulu
P20 Identification of EBV Early Antigen (EA) derived peptides for NPC diagnosis
Theodora Caroline Sihotang, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita
P21 Host-pathogen study: relative expression of mRNA BRLF1 Epstein-Barr virus as a potential biomarker for tumor progressivity and polymorphisms of TCRBC and TCRGC2 host genes related to genetic susceptibility on nasopharyngeal carcinoma
Daniel Joko Wahyono, Purnomo Soeharso, Dwi Anita Suryandari, Lisnawati, Zanil Musa, Bambang Hermani
P22 In vitro efficacy of silvestrol and episilvestrol, isolated from Borneo, on nasopharyngeal carcinoma, a major cancer in Borneo
Maelinda Daker, Yeo Jiun Tzen, Norhasimah Bakar, Asma’ Saiyidatina Aishah Abdul Rahman, Munirah Ahmad, Yeo Tiong Chia, Alan Khoo Soo Beng
P23 The expression of mir-141 in patients with nasopharyngeal cancer
Widyandani Sasikirana, Tirta Wardana, Muhammad Radifar, Cita Herawati, Agus Surono, Sofia Mubarika Haryana
doi:10.1186/s12919-016-0001-5
PMCID: PMC4896251
15.  High HLA-DP Expression and Graft-versus-Host Disease 
The New England journal of medicine  2015;373(7):599-609.
Background
Transplantation of hematopoietic cells from unrelated donors can cure blood disorders but carries a significant risk of acute graft-versus-host disease (GVHD). The risk is higher when the recipient and donor are HLA-DPB1–mismatched, but the mechanisms leading to GVHD are unknown. The HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression. We tested the hypothesis that the GVHD risk correlates with the rs9277534 allele linked to the mismatched HLA-DPB1 in the recipient.
Methods
We genotyped rs9277534 in 3505 persons to define rs9277534-DPB1 haplotypes. Among 1441 recipients of transplants from HLA-A,B,C,DRB1,DQB1–matched unrelated donors with only one HLA-DPB1 mismatch, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined. HLA-DPB1 expression was assessed by means of a quantitative polymerase-chain-reaction assay. The risk of acute GVHD among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534G (high expression) was compared with the risk among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534A (low expression).
Results
The mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, the risk of acute GVHD was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.54; 95% confidence interval [CI], 1.25 to 1.89; P<0.001), as was the risk of death due to causes other than disease recurrence (hazard ratio, 1.25; 95% CI, 1.00 to 1.57; P = 0.05).
Conclusions
The risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1–mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD. (Funded by the National Institutes of Health and others.)
doi:10.1056/NEJMoa1500140
PMCID: PMC4560117  PMID: 26267621
16.  HLA-A is a Predictor of Hepatitis B e Antigen Status in HIV-Positive African Adults 
The Journal of Infectious Diseases  2015;213(8):1248-1252.
Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of human immunodeficiency virus (HIV) coinfection. The factors driving different outcomes are not well understood, but there is increasing interest in an HLA class I effect. We therefore studied the influence of HLA class I on HBV in an African HIV-positive cohort. We demonstrated that virologic markers of HBV disease activity (hepatitis B e antigen status or HBV DNA level) are associated with HLA-A genotype. This finding supports the role of the CD8+ T-cell response in HBV control, and potentially informs future therapeutic T-cell vaccine strategies.
doi:10.1093/infdis/jiv592
PMCID: PMC4799671  PMID: 26655301
HBV; HIV; coinfection; immunology; CD8+ T cells; HLA; HBeAg (hepatitis B e antigen); viral hepatitis; Africa
17.  Relationship of HIV Reservoir Characteristics with Immune Status and Viral Rebound Kinetics in an HIV Therapeutic Vaccine Study 
AIDS (London, England)  2014;28(18):2649-2657.
Objectives
To evaluate the impact of therapeutic HIV vaccination on the HIV reservoir, and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics.
Design
Retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine.
Methods
Participants received vaccine/placebo at weeks 0, 4, and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia (RV) were quantified at weeks 0, 8, and 38. HIV-specific CD4+/CD8+ activity were assessed by an intracellular cytokine staining assay.
Results
At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4+ interferon-γ-producing cells (CA-RNA: r = −0.23, P=0.03 and CA-DNA: r = −0.28, P<0.01, N=93). Therapeutic HIV vaccination induced HIV-specific CD4+ activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable RV at week 8 had higher frequencies of HIV-specific CD4+ and CD8+ interferon-γ-producing cells (undetectable versus detectable RV: 277 versus 161 CD4+ cells/106 lymphocytes, P=0.03 and 1326 versus 669 CD8+ cells/106 lymphocytes, P=0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P<0.01 and CA-DNA: r = 0.47, P<0.01).
Conclusions
Vaccine-induced T-cell responses were associated with a modest transient effect on RV, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics.
doi:10.1097/QAD.0000000000000478
PMCID: PMC4267919  PMID: 25254301
18.  Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa 
PLoS Medicine  2015;12(11):e1001900.
Background
Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure.
Methods and Findings
Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I—presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control.
Conclusions
These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells.
An analysis from a cohort in South Africa reveals how the HIV virus may escape NK cell immunity by acquiring mutations in HLA-mediated epitopes, which affect binding to NK cell receptors.
Editors' Summary
Background
Throughout life, our immune system—a complex network of cells, tissues, and organs—protects us from attack by viruses, bacteria, parasites, and fungi. The body’s first line of defense against these “pathogens” is the innate immune system, a collection of cells and proteins that is always ready to identify and kill a wide range of foreign invaders. As well as directly killing pathogens, the innate immune system activates the adaptive immune response, which recognizes and kills specific pathogens and is responsible for immunological memory. Most pathogens are dispatched quickly and effectively by the two arms of the immune system, but some infectious agents have found ways to evade the immune response. For example, infection with HIV-1, the virus that causes AIDS, results in prolonged, continuous viral replication even though the human body mounts a vigorous HIV-1-specific immune response. In large part, HIV-1’s evasion of the immune response reflects its ability to kill virus-specific CD4 lymphocytes, which are needed to help other immune system cells kill HIV-1-infected cells. In addition, the proteins on the surface of HIV-1 that are recognized by the human immune system (viral antigens) frequently acquire changes (mutations) that make it harder for the immune system to clear HIV-1 from the human body.
Why Was This Study Done?
Viruses evade immune surveillance in many ways, and if we understood the mechanisms underlying immune evasion better, it might be possible to develop targeted immune interventions to deal with viruses such as HIV-1. Here, the researchers investigate how natural killer (NK) cells, a type of lymphocyte that is an important component of the innate antiviral immune response, recognize HIV-infected cells and how HIV-1 evades NK-cell-mediated immune pressure. NK cell activation is determined by the integration of inhibitory and activating signals delivered to the cells by several different receptor families, including the family of killer-cell immunoglobulin-like receptors (KIRs). KIRs mainly bind to human leukocyte antigen (HLA) class I molecules (ligands) on their target cells. HLA class I proteins display fragments (epitopes; peptides recognized by the immune system) of pathogens present in infected cells on the cell surface so that the immune system knows that that cell needs destroying. The binding of distinct KIRs to HLA class I ligands depends on both the sequence of the HLA class I molecule and the sequence of the epitope presented by that HLA class I molecule. Thus, the researchers hypothesized that HIV-1 might evade NK-cell-mediated immune surveillance by acquiring mutations within epitopes presented by HLA class I molecules that enhance the engagement of inhibitory KIRs on NK cells, thereby inhibiting NK cell activity.
What Did the Researchers Do and Find?
To investigate this model, the researchers asked whether any polymorphisms (naturally occurring genetic variations) in the HIV-1 gene encoding the p24 Gag protein were selected on a population level in HIV-1-infected individuals expressing specific combinations of KIRs and HLA class I ligands. Using statistical methods to identify KIR/HLA combined genotypes in a large group of untreated HIV-1-infected individuals from South Africa, they showed that a specific sequence polymorphism in p24 Gag was selected for in individuals expressing both HLA-C*03:04 and KIR2DL3. Functional studies showed that the selection of this variant HIV-1 epitope resulted in better binding of KIR2DL3, an inhibitory KIR, to HLA-C*03:04 than the wild-type epitope. Moreover, the activation of KIR2DL3-positive NK cells from healthy donors in response to HLA-C*03:04-positive target cells presenting the variant epitope was significantly reduced compared to the activation of KIR2DL3-positive NK cells in response to target cells presenting the wild-type epitope.
What Do These Findings Mean?
Further studies are needed to assess the consequences of this and other viral sequence variants for viral fitness, the processing and presentation of the mutant epitope during natural infections, and the control of HIV-1 replication in patients. However, these findings provide new insights into how HIV-1 (and possibly other viruses that have a high mutation rate) might evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance the binding of inhibitory KIRs to HLA class I/peptide complexes. A better understanding of this molecular mechanism for evasion of immune surveillance should facilitate the development of targeted immune interventions (for example, the use of KIR-blocking antibodies, some of which are already being clinically tested for the treatment of cancer) to maximize the antiviral activities of NK cells.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001900.
The US National Institute of Allergy and Infectious Diseases provides a simple description of the human immune system and information on all aspects of HIV infection and AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS; Avert also provides personal stories about living with HIV/AIDS
The British Society for Immunology provides short articles about various aspects of immunology, including general information about host–pathogen interactions and immune evasion and specific information about HIV and immune evasion
Wikipedia has pages on natural killer cells, KIRs, and HLA molecules (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001900
PMCID: PMC4648589  PMID: 26575988
19.  HLA Class I and KIR Genes Do Not Protect Against HIV Type 1 Infection in Highly Exposed Uninfected Individuals With Hemophilia A 
The Journal of Infectious Diseases  2014;210(7):1047-1051.
A recent genome-wide association study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with human immunodeficiency virus type 1 (HIV-1) did not reveal genetic variants associated with resistance to HIV-1 infection, beyond homozygosity for CCR5-Δ32. Since variation in HLA class I and KIR genes is not well interrogated by standard GWAS techniques, we tested whether these 2 loci were involved in protection from HIV-1 infection in the same hemophilia cohort, using controls from the general population. Our data indicate that HLA class I alleles, presence or absence of KIR genes, and functionally relevant combinations of the HLA/KIR genotypes are not involved in resistance to parenterally transmitted HIV-1 infection.
doi:10.1093/infdis/jiu214
PMCID: PMC4215081  PMID: 24719475
HESN; hemophilia; HIV-1; HLA; KIR
20.  Host Genetic and Viral Determinants of HIV-1 RNA Set Point among HIV-1 Seroconverters from Sub-Saharan Africa 
Journal of Virology  2014;89(4):2104-2111.
ABSTRACT
We quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point and R2 to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, and B*27:03) and plasma HIV-1 levels of the transmitting partner, which explained 13% and 10% of variation in set point, respectively. HLA-A concordance between partners and TLR polymorphisms (TLR2 rs3804100 and TLR7 rs179012) also were associated with set point, explaining 6% and 5% of the variation, respectively. Overall, these factors and genital factors of the transmitter (i.e., male circumcision, bacterial vaginosis, and use of acyclovir) explained 46% of variation in set point. We found that both innate and adaptive immune responses, together with plasma HIV-1 levels of the transmitting partner, explain almost half of the variation in viral load set point.
IMPORTANCE After HIV-1 infection, uncontrolled virus replication leads to a rapid increase in HIV-1 concentrations. Once host immune responses develop, however, HIV-1 levels reach a peak and subsequently decline until they reach a stable level that may persist for years. This stable HIV-1 set point represents an equilibrium between the virus and host responses and is predictive of later disease progression and transmission potential. Understanding how host and virus factors interact to determine HIV-1 set point may elucidate novel mechanisms or biological pathways for treating HIV-1 infection. We identified host and virus factors that predict HIV-1 set point in people who recently acquired HIV-1, finding that both innate and adaptive immune responses, along with factors that likely influence HIV-1 virulence and inoculum, explain ∼46% of the variation in HIV-1 set point.
doi:10.1128/JVI.01573-14
PMCID: PMC4338863  PMID: 25473042
21.  High density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis 
Nature genetics  2015;47(2):172-179.
Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn’s disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical HLA molecules1. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but lacked the statistical power to define the architecture of association and causal alleles2,3. To address this, we performed high-density SNP typing of the MHC in >32,000 patients with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn’s disease and ulcerative colitis. Significant differences were observed between these diseases, including a predominant role of class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response to the colonic environment in the pathogenesis of IBD.
doi:10.1038/ng.3176
PMCID: PMC4310771  PMID: 25559196
22.  Sequence variations in HIV-1 p24 Gag-derived epitopes can alter binding of KIR2DL2 to HLA- C*03:04 and modulate primary NK cell function 
AIDS (London, England)  2014;28(10):1399-1408.
OBJECTIVE
The aim of this study was to assess the consequence of sequence variations in HLA-C*03:04-presented HIV-1 p24 Gag epitopes on binding of the inhibitory NK cell receptor KIR2DL2 to HLA-C*03:04.
DESIGN
HIV-1 may possibly evade recognition by KIR+ NK cells through selection of sequence variants that interfere with the interactions of inhibitory KIRs and their target ligands on HIV-1-infected cells. KIR2DL2 is an inhibitory NK cell receptor that binds to a family of HLA-C ligands. Here, we investigated whether HIV-1 encodes for HLA-C*03:04-restricted epitopes that alter KIR2DL2 binding.
METHODS
Tapasin-deficient 721.220 cells expressing HLA-C*03:04 were pulsed with overlapping peptides (10mers overlapping by 9 amino acids, spanning the entire HIV-1 p24 Gag sequence) to identify peptides that stabilized HLA-C expression. Then, the impact that sequence variation in HLA-C*03:04-binding HIV-1 epitopes has on KIR2DL2 binding and KIR2DL2+ NK cell function was determined using KIR2DL2-Fc constructs and NK cell degranulation assays.
RESULTS
Several novel HLA-C*03:04 binding epitopes were identified within the HIV-1 p24 Gag consensus sequence. Three of these consensus sequence peptides (Gag144-152, Gag163-171, and Gag295-304) enabled binding of KIR2DL2 to HLA-C*03:04 and resulted in inhibition of KIR2DL2+ primary NK cells. Furthermore, naturally occurring minor variants of epitope Gag295-304 enhanced KIR2DL2 binding to HLA-C*03:04.
CONCLUSIONS
Our data show that naturally occurring sequence variations within HLA-C*03:04-restricted HIV-1 p24 Gag epitopes can have a significant impact on the binding of inhibitory KIR receptors and primary NK cell function.
doi:10.1097/QAD.0000000000000284
PMCID: PMC4453925  PMID: 24785948
Innate Immunity; HIV-1 epitopes; Natural Killer cell; Killer cell immunoglobulin-like receptor
23.  Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection 
PLoS Pathogens  2015;11(6):e1004954.
HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression.
Author Summary
HLA plays a central role in determining disease outcome in adult HIV infection. A principal mechanism by which this HLA effect is mediated is via viral replicative capacity (VRC), protective HLA alleles such as HLA-B*57 driving the selection of viral escape mutants that reduce VRC. The factors contributing to the diverse disease progression rates observed in infected children, however, remain uncertain. We here address the role of HLA and VRC in pediatric disease progression in a large cohort in Kimberley, South Africa. The findings highlight the consistent and important role of VRC in both adult and pediatric progression. However, the impact of key HLA molecules in shaping disease outcome in adult infection is notably absent in pediatric infection. Further studies of pediatric infection therefore provide the potential to gain critical new insights into HLA-independent mechanisms of HIV disease non-progression that predominate in HIV-infected but healthy, ART-naive children. Understanding these mechanisms remains of direct relevance to the development of future interventions to minimize HIV disease.
doi:10.1371/journal.ppat.1004954
PMCID: PMC4468173  PMID: 26076345
24.  Distinct assembly profiles of HLA-B molecules 
Major histocompatibility complex (MHC) class I polymorphisms are known to influence outcomes in a number of infectious diseases, cancers and inflammatory diseases. Human MHC class I heavy chains are encoded by the HLA-A, HLA-B and HLA-C genes. These genes are highly polymorphic, with the HLA-B locus being the most variable. Each HLA class I protein binds to distinct set of peptide antigens, which are presented to CD8+ T cells. HLA-disease associations have been shown in some cases to link to the peptide binding characteristics of individual HLA class I molecules. Here we show that polymorphisms at the HLA-B locus profoundly influence the assembly characteristics of HLA-B molecules and the stabilities of their peptide-deficient forms. In particular, dependence on the assembly factor tapasin is highly variable, with frequent occurrence of strongly tapasin-dependent or independent allotypes. Several polymorphic HLA-B residues located near the C-terminal end of the peptide are key determinants of tapasin-independent assembly. In vitro refolded forms of tapasin-independent allotypes assemble more readily with peptides compared to tapasin-dependent allotypes that belong to the same supertype, and during refolding, reduced aggregation of tapasin-independent allotypes is observed. Paradoxically, in HIV-infected individuals, greater tapasin-independent HLA-B assembly confers more rapid progression to death, consistent with previous findings that some HLA-B allotypes shown to be tapasin-independent are associated with rapid progression to multiple AIDS outcomes. Together, these findings demonstrate significant variations in the assembly of HLA-B molecules, and indicate influences of HLA-B folding patterns upon infectious disease outcomes.
doi:10.4049/jimmunol.1301670
PMCID: PMC4117407  PMID: 24790147
25.  Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome 
Journal of Virology  2014;88(21):12793-12801.
ABSTRACT
Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral set point have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1. A total of 620 individuals with primary HIV-1 infection were screened by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay for HLA class I-restricted, epitope-specific CD8 T cell responses using optimally defined epitopes approximately 2 months after initial presentation. The cohort was predominantly male (97%) and Caucasian (83%) (Fiebig stages II/III [n = 157], IV [n = 64], V [n = 286], and VI [n = 88] and Fiebig stage not determined [n = 25]). Longitudinal viral loads, CD4 count, and time to ART were collected for all patients. We observed strong associations between viral load at baseline (initial viremia) and the established early viral set points (P < 0.0001). Both were significantly associated with HLA class I genotypes (P = 0.0009). While neither the breadth nor the magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag during primary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses—but not others—significantly influenced the time to ART initiation. Individual epitope-specific CD8 T cell responses contribute significantly to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of antiviral function.
IMPORTANCE Understanding which factors are involved in the control of HIV-1 infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here, using a cohort of over 600 individuals with acute and early HIV-1 infection, we assessed in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV-1 to control of viremia and their impact on the overall course of disease progression.
doi:10.1128/JVI.02016-14
PMCID: PMC4248916  PMID: 25165102

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