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1.  Proceedings of the Canadian society of allergy and clinical immunology annual scientific meeting 2015 
Côté, Marie-Ève | Boulay, Marie-Ève | Plante, Sophie | Chakir, Jamila | Boulet, Louis-Philippe | Ahmed, Hanan | Ospina, Maria-Beatriz | Sideri, Kyriaki | Vliagoftis, Harissios | Johnson, Sara F. | Woodgate, Roberta L. | Cros, Guilhem | Teira, Pierre | Cellot, Sonia | Bittencourt, Henrique | Decaluwe, Helene | Vachon, Marie France | Duval, Michel | Haddad, Elie | Kim, Vy H. D. | Pham-Huy, Anne | Grunebaum, Eyal | Oliveria, John-Paul | Phan, Stephanie | Tenn, Mark W. | Tworek, Damian | Smith, Steven G. | Baatjes, Adrian J. | Obminski, Caitlin D. | Munoz, Caroline E. | Scime, Tara X. | Sehmi, Roma | Gauvreau, Gail M. | Salter, Brittany M. | Smith, Steven G. | Obminski, Caitlin D. | Munoz, Caroline E. | Schlatman, Abbey | Scime, Tara X. | Watson, Rick | Sherkat, Roya | Khoshnevisan, Razieh | Sheikhbahaei, Saba | Betschel, Stephen | Warrington, Richard | Schellenberg, Robert | Fein, Michael N. | Pelletier, Jean-Philippe | Kan, Manstein | Labrosse, Roxane | Mak, Raymond | Loh, James | Kanani, Amin | Nowak, Dominik A. | Keith, Paul K. | Pannozzo, Daniel | Lima, Hermenio C. | Pham, Diana | Pham, Hoang | Alvarez, Gonzalo G. | Bencze, Istvan T. | Sharma, Krishna B. | Smith, Mark | Aaron, Shawn | Block, Jennifer | Keays, Tara | Leech, Judith | Schneidermen, David | Cameron, Jodi | Forgie, Jennifer | Ring, Alicia | O’Quinn, John W. | Santucci, Stephanie | Yang, William H. | Gaudet, Ena | Aaron, Shawn | Voisin, Mathew R. | Borici-Mazi, Rozita | Vostretsova, Kateryna | Stark, Donald F. | Yeboah, Elizabeth | Martin-Rhee, Michelle | Gula, Cheryl | Cheng, Clare | Paltser, Geoff | Dery, Alizée | Clarke, Ann | Nadeau, Kari | Harada, Laurie | Weatherall, Kimberley | Greenwood, Celia | Daley, Denise | Asai, Yuka | Ben-Shoshan, Moshe | Ling, Ling | Ospina, Maria B. | Protudjer, Jennifer L. P. | Vetander, Mirja | van Hage, Marianne | Olén, Ola | Wickman, Magnus | Bergström, Anna | Teoh, Timothy | Mill, Christopher | Wong, Tiffany | Baerg, Ingrid | Alexander, Angela | Hildebrand, Kyla J. | Dean, John | Kuzeljevic, Boris | Chan, Edmond S. | Argeny, Jonathan | Gona-Hoepler, Mia | Fucik, Petra | Nachbaur, Edith | Gruber, Saskia | Crameri, Reto | Glaser, Andreas | Szépfalusi, Zsolt | Rhyner, Claudio | Eiwegger, Thomas | Plunkett, Greg | Mire, Brad | Yazicioglu, Mehtap | Can, Ceren | Ciplak, Gokce | Cook, Victoria E. | Portales-Casamar, Elodie | Nashi, Emil P. | Gabrielli, Sofianne | Primeau, Marie-Noel | Lejtenyi, Christine | Netchiporouk, Elena | Dery, Alizee | Shand, Greg | Hoe, Erica | Liem, Joel | Ko, Jason K. | Huang, David J. T. | Mazza, Jorge A. | McHenry, Mary | Otley, Anthony | Watson, Wade | Kraft, John N. | Paina, Mihaela | Darwish Hassan, Ahmed A. | Heroux, Delia | Crawford, Lynn | Gauvreau, Gail | Denburg, Judah | Pedder, Linda | Chad, Zave | Sussman, Gordon | Hébert, Jacques | Frankish, Charles | Olynych, Timothy | Cheema, Amarjit | Del Carpio, Jaime | Harrison, Rachel | Torabi, Bahar | Medoff, Elaine | Mill, Jennifer | Quirt, Jaclyn A. | Wen, Xia | Kim, Jonathan | Herrero, Angel Jimenez | Kim, Harold L. | Grzyb, Magdalena J. | Primeau, Marie-Noël | Azad, Meghan B. | Lu, Zihang | Becker, Allan B. | Subbarao, Padmaja | Mandhane, Piushkumar J. | Turvey, Stuart E. | Sears, Malcolm R. | Boucher-Lafleur, Anne-Marie | Gagné-Ouellet, Valérie | Jacques, Éric | Laprise, Catherine | Chen, Michael | McGovern, Toby | Adner, Mikael | Martin, James G. | Cosic, Nela | Ntanda, Henry | Giesbrecht, Gerald | Kozyrskyj, Anita | Letourneau, Nicole | Dawod, Bassel | Marshall, Jean | De Schryver, Sarah | Halbrich, Michelle | La Vieille, Sebastian | Eisman, Harley | Alizadehfar, Reza | Joseph, Lawrence | Morris, Judy | Feldman, Laura Y. | Thacher, Jesse D. | Kull, Inger | Melén, Erik | Pershagen, Göran | Protudjer, Jennifer L. P. | Hosseini, Ali | Hackett, Tillie L. | Hirota, Jeremy | McNagny, Kelly | Wilson, Susan | Carlsten, Chris | Huq, Saiful | Chooniedass, Rishma | Gerwing, Brenda | Huang, Henry | Lefebvre, Diana | Becker, Allan | Khamis, Mona M. | Awad, Hanan | Allen, Kevin | Adamko, Darryl J. | El-Aneed, Anas | Kim, Young Woong | Gliddon, Daniel R. | Shannon, Casey P. | Singh, Amrit | Hickey, Pascal L. C. | Ellis, Anne K. | Neighbour, Helen | Larche, Mark | Tebbutt, Scott J. | Ladouceur, Erika | Stewart, Miriam | Evans, Josh | Masuda, Jeff | To, Teresa | King, Malcolm | Larouche, Miriam | Liang, Liming | Legere, Stephanie A. | Haidl, Ian D. | Legaré, Jean-Francois | Marshall, Jean S. | Sears, Malcolm | Moraes, Theo J. | Ratjen, Felix | Gustafsson, Per | Lou, Wendy | North, Michelle L. | Lee, Elizabeth | Omana, Vanessa | Thiele, Jenny | Brook, Jeff | Rahman, Tanvir | Lejtenyi, Duncan | Fiter, Ryan | Piccirillo, Ciriaco | Mazer, Bruce | Simons, Elinor | Hildebrand, Kyla | Turvey, Stuart | DeMarco, Mari | Le Cao, Kim-Anh | Gauvreau, Gail M. | Mark FitzGerald, J. | O’Byrne, Paul M. | Stiemsma, Leah T. | Arrieta, Marie-Claire | Cheng, Jasmine | Dimitriu, Pedro A. | Thorson, Lisa | Yurist, Sophie | Lefebvre, Diana L. | Mandhane, Piush | McNagny, Kelly M. | Kollmann, Tobias | Mohn, William W. | Brett Finlay, B. | Tran, Maxwell M. | Lefebvre, Diana L. | Ramasundarahettige, Chinthanie F. | Dai, Wei Hao | Mandhane, Piush J. | Tworek, Damian | O’Byrne, Seamus N. | O’Byrne, Paul M. | Denburg, Judah A. | Walsh, Laura | Soliman, Mena | Steacy, Lisa M. | Adams, Daniel E. | Warner, Linda | Mauro, Mary Ann | Mamonluk, Robby | Yang, ChenXi | Conway, Ed M.
Table of contents
A1 Role of fibrocytes in allergic rhinitis
Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet
A2 Patterns of aeroallergens sensitization in Northern Alberta
Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis
A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA)
Sara F. Johnson, Roberta L. Woodgate
A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease
Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad
A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario
Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum
A6 Detection of regulatory B cells in the airways of subjects with asthma
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Damian Tworek, Steven G. Smith, Adrian J. Baatjes, Caitlin D. Obminski, Caroline E. Munoz, Tara X. Scime, Roma Sehmi, Gail M Gauvreau
A7 Characterization of IgE-expressing B cells in the airways and peripheral blood of allergic asthmatic subjects
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Brittany M Salter, Steven G Smith, Caitlin D Obminski, Caroline E Munoz, Abbey Schlatman, Tara X Scime, Rick Watson, Roma Sehmi, Gail M Gauvreau
A8 Pregnancy: could it be a risk factor for primary immunodeficient patients
Roya Sherkat, Razieh Khoshnevisan, Saba Sheikhbahaei
A9 Clinical experience with Octagam: a Canadian retrospective chart review
Stephen Betschel, Richard Warrington, Robert Schellenberg
A10 Kounis syndrome secondary to contrast media with inferior ST elevations and bilateral ischemic stroke
Michael N Fein, Jean-Philippe Pelletier
A11 Honey bee venom immunotherapy ineffective in bumble bee-induced anaphylaxis: case report and review of literature
Manstein Kan, Robert Schellenberg
A12 Delayed immune reconstitution occurring after multiple immune complications of hematological stem cell transplantation for a leaky SCID
Roxane Labrosse, Guilhem Cros, Pierre Teira, Henrique Bittencourt, Helene Decaluwe, Michel Duval, Elie Haddad
A13 Comparison of Three Case Reports of Acquired Angioedema: presentation, management and outcome
Raymond Mak, James Loh, Amin Kanani
A14 Sitagliptin-associated angioedema not related to concurrent use of ARB or ACE inhibitor
Dominik A. Nowak, Paul K. Keith
A15 Sneddon-Wilkinson subcorneal pustular dermatosis associated with an IgA monoclonal gammopathy
Daniel Pannozzo, Dominik A. Nowak, Hermenio C. Lima
A16 Omalizumab can be effective in patients with allergic bronchopulmonary aspergillosis
Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, John W. O’Quinn, Stephanie Santucci, William H. Yang
A17 Efficacious use of omalizumab in the treatment of cystic fibrosis
Diana Pham, Hoang Pham, Ena Gaudet, Shawn Aaron, Stephanie Santucci, William H. Yang
A18 HAE with normal C1-INH with inconsistent response to C1 esterase inhibitor infusion but reliably responsive to icatibant
Hoang Pham, Stephanie Santucci, William H. Yang
A19 Anaphylaxis reaction to lactase enzyme
Mathew R. Voisin, Rozita Borici-Mazi
A20 Risk of solid tumor malignancies in patients with primary immune deficiency
Kateryna Vostretsova, Donald F. Stark
A21 Is it time to adopt the chromogenic assay for measuring C1 esterase inhibitor function in patients with HAE Type 2?
Elizabeth Yeboah, Paul K. Keith
A22 Emergency department visits for anaphylaxis and allergic reactions
Michelle Martin-Rhee, Cheryl Gula, Clare Cheng, Geoff Paltser
A23 START: Susceptibility To food Allergies in a Registry of Twins
Alizée Dery, Ann Clarke, Kari Nadeau, Laurie Harada, Kimberley Weatherall, Celia Greenwood, Denise Daley, Yuka Asai, Moshe Ben-Shoshan
A24 Qualifying the diagnostic approach employed by allergists when managing patients with self-diagnosed non-celiac gluten sensitivity (NCGS)
Lee Horgan, Teresa Pun
A25 Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody in adults with suspected food allergy
Ling Ling, Maria B. Ospina, Kyriaki Sideri, Harissios Vliagoftis
A26 Staple food hypersensitivity from infancy to adolescence: a report from the BAMSE cohort
Jennifer L.P. Protudjer, Mirja Vetander, Marianne van Hage, Ola Olén, Magnus Wickman, Anna Bergström
A27 Evaluating the impact of supervised epinephrine autoinjector administration during food challenges on perceived parent confidence
Timothy Teoh, Christopher Mill, Tiffany Wong, Ingrid Baerg, Angela Alexander, Kyla J. Hildebrand, John Dean, Boris Kuzeljevic, Edmond S. Chan
A28 Local immunoglobulin production to Aspergillus fumigatus cystic fibrosis
Jonathan Argeny, Mia Gona-Hoepler, Petra Fucik, Edith Nachbaur, Saskia Gruber, Reto Crameri, Andreas Glaser, Zsolt Szépfalusi, Claudio Rhyner, Thomas Eiwegger
A29 Extract consumption with skin prick test (SPT) devices
Greg. Plunkett, Brad Mire
A30 Evaluation of our cases with nonsteroidal anti-inflammatory drug reactions
Mehtap Yazicioglu, Ceren Can, Gokce Ciplak
A31 Reasons for referral and final diagnoses in a tertiary care pediatric allergy clinic
Victoria E. Cook, Kyla J. Hildebrand, Elodie Portales-Casamar, Christopher Mill, Edmond S. Chan
A32 Internist referral practices for inpatients with self-reported penicillin allergies at a tertiary care teaching hospital
Michael N Fein, Emil P Nashi
A33 Assessing the risk of reactions in children with a negative oral challenge after a subsequent use of amoxicillin
Sofianne Gabrielli, Christopher Mill, Marie-Noel Primeau, Christine Lejtenyi, Elena Netchiporouk, Alizee Dery, Greg Shand, Moshe Ben-Shoshan
A34 Validity of self-reported penicillin allergies
Erica Hoe, Joel Liem
A35 Effectiveness of allergy-test directed elimination diets in eosinophilic esophagitis
Jason K. Ko, David J.T. Huang, Jorge A. Mazza
A36 Allergy testing and dietary management in pediatric eosinophilic esophagitis (EoE): A retrospective review of a tertiary Canadian centre’s experience
Mary McHenry, Anthony Otley,Wade Watson
A37 Visualizing the impact of atopic and allergic skin disease
Dominik A. Nowak, John N. Kraft
A38 Cystic fibrosis with and without nasal polyposis in pediatric patients: a cross-sectional comparative study
Mihaela Paina, Ahmed A. Darwish Hassan, Delia Heroux, Lynn Crawford, Gail Gauvreau, Judah Denburg, Linda Pedder, Paul K. Keith
A39 Evaluation of macrolide antibiotic hypersensitivity: the role of oral challenges in children
Bahar Torabi, Marie-Noel Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A40 Venom allergy testing: is a graded approach necessary?
Jaclyn A. Quirt, Xia Wen, Jonathan Kim, Angel Jimenez Herrero, Harold L. Kim
A41 The role of oral challenges in evaluating cephalosporin hypersensitivity reactions in children
Magdalena J. Grzyb, Marie-Noël Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A42 Breastfeeding and infant wheeze, atopy and atopic dermatitis: findings from the Canadian Healthy Infant Longitudinal Development Study
Meghan B. Azad, Zihang Lu, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, the CHILD Study Investigators
A43 IL33 DNA methylation in bronchial epithelial cells is associated to asthma
Anne-Marie Boucher-Lafleur, Valérie Gagné-Ouellet, Éric Jacques, Sophie Plante, Jamila Chakir, Catherine Laprise
A44 NRF2 mediates the antioxidant response to organic dust-induced oxidative stress in bronchial epithelial cells
Michael Chen, Toby McGovern, Mikael Adner, James G. Martin
A45 The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months
Nela Cosic, Henry Ntanda, Gerald Giesbrecht, Anita Kozyrskyj, Nicole Letourneau
A46 Examining the immunological mechanisms associated with cow’s milk allergy
Bassel Dawod, Jean Marshall
A47 Tryptase levels in children presenting with anaphylaxis to the Montréal Children’s Hospital
Sarah De Schryver, Michelle Halbrich, Ann Clarke, Sebastian La Vieille, Harley Eisman, Reza Alizadehfar, Lawrence Joseph, Judy Morris, Moshe Ben-Shoshan
A48 Secondhand tobacco smoke exposure in infancy and the development of food hypersensitivity from childhood to adolescence
Laura Y. Feldman, Jesse D. Thacher, Inger Kull, Erik Melén, Göran Pershagen, Magnus Wickman, Jennifer L. P. Protudjer, Anna Bergström
A49 Combined exposure to diesel exhaust and allergen enhances allergic inflammation in the bronchial submucosa of atopic subjects
Ali Hosseini, Tillie L. Hackett, Jeremy Hirota, Kelly McNagny, Susan Wilson, Chris Carlsten
A50 Comparison of skin-prick test measurements by an automated system against the manual method
Saiful Huq, Rishma Chooniedass, Brenda Gerwing, Henry Huang, Diana Lefebvre, Allan Becker
A51 The accurate identification and quantification of urinary biomarkers of asthma and COPD through the use of novel DIL- LC-MS/MS methods
Mona M. Khamis, Hanan Awad, Kevin Allen, Darryl J. Adamko, Anas El-Aneed
A52 Systemic immune pathways associated with the mechanism of Cat-Synthetic Peptide Immuno-Regulatory Epitopes, a novel immunotherapy, in whole blood of cat-allergic people
Young Woong Kim, Daniel R. Gliddon, Casey P. Shannon, Amrit Singh, Pascal L. C. Hickey, Anne K. Ellis, Helen Neighbour, Mark Larche, Scott J. Tebbutt
A53 Reducing the health disparities: online support for children with asthma and allergies from low-income families
Erika Ladouceur, Miriam Stewart, Josh Evans, Jeff Masuda, Nicole Letourneau, Teresa To, Malcolm King
A54 Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study
Miriam Larouche, Liming Liang, Catherine Laprise
A55 IL-33 induces cytokine and chemokine production in human mast cells
Stephanie A. Legere, Ian D. Haidl, Jean-Francois Legaré, Jean S. Marshall
A56 Reference ranges for lung clearance index from infancy to adolescence for Canadian population
Zihang Lu, Malcolm Sears, Theo J. Moraes, Felix Ratjen, Per Gustafsson, Wendy Lou, Padmaja Subbarao
A57 Kingston Allergy Birth Cohort: cohort profile and mother/child characteristics to age 2
Michelle L. North, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Jeff Brook, Anne K. Ellis
A58 Cow’s milk protein specific IgE, IgA and IgG4 as a predictor of outcome in oral immunotherapy
Tanvir Rahman, Duncan Lejtenyi, Sarah De Schryver, Ryan Fiter, Ciriaco Piccirillo, Moshe Ben-Shoshan, Bruce Mazer
A59 Age of peanut introduction and development of reactions and sensitization to peanut
Elinor Simons, Allan B. Becker, Rishma Chooniedass, Kyla Hildebrand, Edmond S. Chan, Stuart Turvey, Padmaja Subbarao, Malcolm Sears
A60 Multi-omic blood biomarker signatures of the late phase asthmatic response
Amrit Singh, Casey P. Shannon, Young Woong Kim, Mari DeMarco, Kim-Anh Le Cao, Gail M. Gauvreau, J. Mark FitzGerald, Louis-Philippe Boulet, Paul M. O’Byrne, Scott J. Tebbutt
A61 Early life gut microbial alterations in children diagnosed with asthma by three years of age
Leah T. Stiemsma, Marie-Claire Arrieta, Jasmine Cheng, Pedro A. Dimitriu, Lisa Thorson, Sophie Yurist, Boris Kuzeljevic, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm R. Sears, Kelly M. McNagny, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, B. Brett Finlay, Stuart E. Turvey
A62 The relationship between food sensitization and atopic dermatitis at age 1 year in a Canadian birth cohort
Maxwell M. Tran, Diana L. Lefebvre, Chinthanie F. Ramasundarahettige, Allan B. Becker, Wei Hao Dai, Padmaja Subbarao, Piush J. Mandhane, Stuart E. Turvey, Malcolm R. Sears
A63 Allergen inhalation enhances Toll-like receptor-induced thymic stromal lymphopoietin receptor expression by hematopoietic progenitor cells in mild asthmatics
Damian Tworek, Delia Heroux, Seamus N. O’Byrne, Paul M. O’Byrne, Judah A. Denburg
A64 The Allergic Rhinitis Clinical Investigator Collaborative – replicated eosinophilia on repeated cumulative allergen challenges in nasal lavage samples
Laura Walsh, Mena Soliman, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis
A65 The CHILD Study: optimizing subject retention in pediatric longitudinal cohort research
Linda Warner, Mary Ann Mauro, Robby Mamonluk, Stuart E. Turvey
A66 Differential expression of C3a and C5a in allergic asthma
ChenXi Yang, Amrit Singh, Casey P. Shannon, Young Woong Kim, Ed M. Conway, Scott J. Tebbutt
doi:10.1186/s13223-016-0118-0
PMCID: PMC5009563
2.  Respiratory syncytial virus-neutralizing serum antibody titers in infants following palivizumab prophylaxis with an abbreviated dosing regimen 
PLoS ONE  2017;12(4):e0176152.
Background
Monthly injections of palivizumab during the respiratory syncytial virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations. However, the additive effect of naturally acquired immunity remains unclear. The objective of this study was to assess total neutralizing serum antibodies (NAb) against RSV in at-risk infants who had received an abbreviated course of palivizumab prophylaxis.
Methods
Serum samples were collected from infants enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2 consecutive RSV seasons (2013 to 2015). Infants in this program had received an abbreviated course of palivizumab in accordance with the provincial guidelines. Data were compared to adults and infants less than 12 months of age who did not receive palivizumab. Anti-RSV NAb titers were measured using an RSV microneutralization assay.
Findings
Infants who received palivizumab had anti-RSV NAb titers at the end of the RSV season that persisted beyond what is expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the control infants who did not receive palivizumab and all tested adults had protective anti-RSV NAb titers.
Conclusions
Based on our observations, we hypothesize that naturally acquired NAb provide additive protection, which may significantly reduce the need for additional doses of palivizumab in infants at risk of severe RSV infections.
doi:10.1371/journal.pone.0176152
PMCID: PMC5402955  PMID: 28437470
3.  Does the impact of a plant-based diet during pregnancy on birth weight differ by ethnicity? A dietary pattern analysis from a prospective Canadian birth cohort alliance 
BMJ Open  2017;7(11):e017753.
Objective
Birth weight is an indicator of newborn health and a strong predictor of health outcomes in later life. Significant variation in diet during pregnancy between ethnic groups in high-income countries provides an ideal opportunity to investigate the influence of maternal diet on birth weight.
Setting
Four multiethnic birth cohorts based in Canada (the NutriGen Alliance).
Participants
3997 full-term mother–infant pairs of diverse ethnic groups who had principal component analysis-derived diet pattern scores—plant-based, Western and health-conscious—and birth weight data.
Results
No associations were identified between the Western and health-conscious diet patterns and birth weight; however, the plant-based dietary pattern was inversely associated with birth weight (β=−67.6 g per 1-unit increase; P<0.001), and an interaction with non-white ethnicity and birth weight was observed. Ethnically stratified analyses demonstrated that among white Europeans, maternal consumption of a plant-based diet associated with lower birth weight (β=−65.9 g per 1-unit increase; P<0.001), increased risk of small-for-gestational age (SGA; OR=1.46; 95% CI 1.08 to 1.54;P=0.005) and reduced risk of large-for-gestational age (LGA; OR=0.71; 95% CI 0.53 to 0.95;P=0.02). Among South Asians, maternal consumption of a plant-based diet associated with a higher birth weight (β=+40.5 g per 1-unit increase; P=0.01), partially explained by cooked vegetable consumption.
Conclusions
Maternal consumption of a plant-based diet during pregnancy is associated with birth weight. Among white Europeans, a plant-based diet is associated with lower birth weight, reduced odds of an infant born LGA and increased odds of SGA, whereas among South Asians living in Canada, a plant-based diet is associated with increased birth weight.
doi:10.1136/bmjopen-2017-017753
PMCID: PMC5695448  PMID: 29138203
nutrition; diet pattern; PCA; birth weight
5.  Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and Combined Impacts on Gut Microbial Changes in Later Infancy 
Established during infancy, our complex gut microbial community is shaped by medical interventions and societal preferences, such as cesarean section, formula feeding, and antibiotic use. We undertook this study to apply the significance analysis of microarrays (SAM) method to quantify changes in gut microbial composition during later infancy following the most common birth and postnatal exposures affecting infant gut microbial composition. Gut microbiota of 166 full-term infants in the Canadian Healthy Infant Longitudinal Development birth cohort were profiled using 16S high-throughput gene sequencing. Infants were placed into groups according to mutually exclusive combinations of birth mode (vaginal/cesarean birth), breastfeeding status (yes/no), and antibiotic use (yes/no) by 3 months of age. Based on repeated permutations of data and adjustment for the false discovery rate, the SAM statistic identified statistically significant changes in gut microbial abundance between 3 months and 1 year of age within each infant group. We observed well-known patterns of microbial phyla succession in later infancy (declining Proteobacteria; increasing Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding, and no antibiotic exposure. Genus Lactobacillus, Roseburia, and Faecalibacterium species appeared in the top 10 increases to microbial abundance in these infants. Deviations from this pattern were evident among infants with other perinatal co-exposures; notably, the largest number of microbial species with unchanged abundance was seen in gut microbiota following early cessation of breastfeeding in infants. With and without antibiotic exposure, the absence of a breast milk diet by 3 months of age following vaginal birth yielded a higher proportion of unchanged abundance of Bacteroidaceae and Enterobacteriaceae in later infancy, and a higher ratio of unchanged Enterobacteriaceae to Alcaligenaceae microbiota. Gut microbiota of infants born vaginally and exclusively formula fed became less enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels of Ruminococcaceae, and exhibited a greater decline in the Rikenellaceae/Bacteroidaceae ratio compared to their breastfed, vaginally delivered counterparts. These changes were also evident in cesarean-delivered infants to a lesser extent. The clinical relevance of these trajectories of microbial change is that they culminate in taxon-specific abundances in the gut microbiota of later infancy, which we and others have observed to be associated with food sensitization.
doi:10.3389/fped.2017.00200
PMCID: PMC5622971
infant gut microbiota; significance analysis of microarrays; cesarean birth; breastfeeding; antibiotic use; food sensitization
6.  Growth and weight gain in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort 
Background
With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.
Methods
Canadian children newly-diagnosed with JIA 2005–2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth.
Results
One thousand one hundred forty seven children were followed for median 35.5 months. Mean Z-scores, and the point prevalence of short stature (height < 2.5th percentile, 2.5% to 3.4%) and obesity (BMI > 95th percentile, 15.8% to 16.4%) remained unchanged in the whole cohort. Thirty-three children (2.9%) developed new-onset short stature, while 27 (2.4%) developed tall stature (>97.5th percentile). Children with systemic arthritis (n = 77) had an estimated 3-year cumulative incidence of 9.3% (95%CI: 4.3–19.7) for new-onset short stature and 34.4% (23–49.4) for obesity. Most children (81.7%) received no systemic corticosteroids, but 1 mg/Kg/day prednisone-equivalent maintained for 6 months corresponded to a drop of 0.64 height Z-scores (0.56–0.82) and an increase of 0.74 BMI Z-scores (0.56–0.92). An increase of 1 in the 10-cm physician global assessment of disease activity maintained for 6 months corresponded to a drop of 0.01 height Z-scores (0–0.02).
Conclusions
Most children in this modern JIA cohort grew and gained weight as children in the general population. About 1 in 10 children who had systemic arthritis, uncontrolled disease and/or prolonged corticosteroid use, had increased risk of growth impairment.
Electronic supplementary material
The online version of this article (doi:10.1186/s12969-017-0196-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s12969-017-0196-7
PMCID: PMC5567720  PMID: 28830457
Juvenile arthritis; Growth; Obesity; Corticosteroids
7.  In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory? 
PLoS ONE  2017;12(6):e0177813.
Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20–57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50–100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy.
doi:10.1371/journal.pone.0177813
PMCID: PMC5479559  PMID: 28636613
8.  A humanized microbiota mouse model of ovalbumin-induced lung inflammation 
Gut Microbes  2016;7(4):342-352.
ABSTRACT
There is increasing evidence for a role of early life gut microbiota in later development of asthma in children. In our recent study, children with reduced abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia had an increased risk of development of asthma and addition of these bacteria in a humanized mouse model reduced airway inflammation. In this Addendum, we provide additional data on the use of a humanized gut microbiota mouse model to study the development of asthma in children, highlighting the differences in immune development between germ-free mice colonized with human microbes compared to those colonized with mouse gut microbiota. We also demonstrate that there is no association between the composition of the gut microbiota in older children and the diagnosis of asthma, further suggesting the importance of the gut microbiota-immune system axis in the first 3 months of life.
doi:10.1080/19490976.2016.1182293
PMCID: PMC4988436  PMID: 27115049
asthma; germ-free mice; gut microbiota; infants; lung
9.  Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016 
Alsayegh, Mohammad A. | Alshamali, Hanan | Khadada, Mousa | Ciccolini, Amanda | Ellis, Anne K. | Quint, Diana | Powley, William | Lee, Laurie | Fiteih, Yahya | Baksh, Shairaz | Vliagoftis, Harissios | Gerega, Sebastien K. | Millson, Brad | Charland, Katia | Barakat, Stephane | Sun, Xichun | Jimenez, Ricardo | Waserman, Susan | FitzGerald, Mark J. | Hébert, Jacques | Cognet-Sicé, Josiane | Renahan, Kevin E. | Huq, Saiful | Chooniedass, Rishma | Sawyer, Scott | Pasterkamp, Hans | Becker, Allan | Smith, Steven G. | Zhang, Shiyuan | Jayasundara, Kavisha | Tacon, Claire | Simidchiev, Alex | Nadeau, Gilbert | Gunsoy, Necdet | Mullerova, Hana | Albers, Frank | Kim, Young Woong | Shannon, Casey P. | Singh, Amrit | Neighbour, Helen | Larché, Mark | Tebbutt, Scott J. | Klopp, Annika | Vehling, Lorena | Becker, Allan B. | Subbarao, Padmaja | Mandhane, Piushkumar J. | Turvey, Stuart E. | Sears, Malcolm R. | Azad, Meghan B. | Loewen, Keely | Monchka, Barret | Mahmud, Salaheddin M. | Jong, Geert ‘t | Longo, Cristina | Bartlett, Gillian | Ducharme, Francine M. | Schuster, Tibor | MacGibbon, Brenda | Barnett, Tracie | North, Michelle L. | Brook, Jeff | Lee, Elizabeth | Omana, Vanessa | Thiele, Jenny | Steacy, Lisa M. | Evans, Greg | Diamond, Miriam | Sussman, Gordon L. | Amistani, Yann | Abiteboul, Kathy | Tenn, Mark W. | Yang, ChenXi | Carlsten, Christopher | Conway, Edward M. | Mack, Douglas | Othman, Yasmin | Barber, Colin M. | Kalicinsky, Chrystyna | Burke, Andrea E. | Messieh, Mary | Nair, Parameswaran | Che, Chun T. | Douglas, Lindsay | Liem, Joel | Duan, Lucy | Miller, Charlotte | Dupuis, Pascale | Connors, Lori A. | Fein, Michael N. | Shuster, Joseph | Hadi, Hani | Polk, Brooke | Raje, Nikita | Labrosse, Roxane | Bégin, Philippe | Paradis, Louis | Roches, Anne Des | Lacombe-Barrios, Jonathan | Mishra, Sanju | Lacuesta, Gina | Chiasson, Meredith | Haroon, Babar | Robertson, Kara | Issekutz, Thomas | Leddin, Desmond | Couban, Stephen | Connors, Lori | Roos, Adrienne | Kanani, Amin | Chan, Edmond S. | Schellenberg, Robert | Rosenfield, Lana | Cvetkovic, Anna | Woodward, Kevin | Quirt, Jaclyn | Watson, Wade T. A. | Castilho, Edson | Sullivan, Jennifer A. | Temple, Beverley | Martin, Donna | Cook, Victoria E. | Mills, Christopher | Portales-Casamar, Elodie | Fu, Lisa W. | Ho, Alexander | Zaltzman, Jeffrey | Chen, Lucy | Vadas, Peter | Gabrielli, Sofianne | Clarke, Ann | Eisman, Harley | Morris, Judy | Joseph, Lawrence | LaVieille, Sebastien | Ben-Shoshan, Moshe | Graham, François | Barnes, Charles | Portnoy, Jay | Stagg, Vincent | Simons, Elinor | Lefebvre, Diana | Dai, David | Mandhane, Piushkumar | Sears, Malcolm | Tam, Herman | Simons, F. Estelle R. | Alotaibi, Dhaifallah | Dawod, Bassel | Tunis, Matthew C. | Marshall, Jean | Desjardins, Marylin | Béland, Marianne | Lejtenyi, Duncan | Drolet, Jean-Phillipe | Lemire, Martine | Tsoukas, Christos | Noya, Francisco J.D. | Alizadehfar, Reza | McCusker, Christine T. | Mazer, Bruce D. | Maestre-Batlle, Danay | Gunawan, Evelyn | Rider, Christopher F. | Bølling, Anette K. | Pena, Olga M. | Suez, Daniel | Melamed, Isaac | Hussain, Iftikhar | Stein, Mark | Gupta, Sudhir | Paris, Kenneth | Fritsch, Sandor | Bourgeois, Christelle | Leibl, Heinz | McCoy, Barbara | Noel, Martin | Yel, Leman | Scott, Ori | Reid, Brenda | Atkinson, Adelle | Kim, Vy Hong-Diep | Roifman, Chaim M. | Grunebaum, Eyal | AlSelahi, Eiman | Aleman, Fernando | Oberle, Amber | Trus, Mike | Sussman, Gordon | Kanani, Amin S. | Chambenoi, Olivier | Chiva-Razavi, Sima | Grodecki, Savannah | Joshi, Nikhil | Menikefs, Peter | Holt, David | Pun, Teresa | Tworek, Damian | Hanna, Raphael | Heroux, Delia | Rosenberg, Elli | Stiemsma, Leah | Turvey, Stuart | Denburg, Judah | Mill, Christopher | Teoh, Timothy | Zimmer, Preeti | Avinashi, Vishal | Paina, Mihaela | Darwish Hassan, Ahmed A. | Oliveria, John Paul | Olesovsky, Chris | Gauvreau, Gail | Pedder, Linda | Keith, Paul K. | Plunkett, Greg | Bolner, Michelle | Pourshahnazari, Persia | Stark, Donald | Vostretsova, Kateryna | Moses, Andrew | Wakeman, Andrew | Singer, Alexander | Gerstner, Thomas | Abrams, Elissa | Johnson, Sara F. | Woodgate, Roberta L.
doi:10.1186/s13223-017-0192-y
PMCID: PMC5390240
10.  Exposure to household furry pets influences the gut microbiota of infant at 3–4 months following various birth scenarios 
Microbiome  2017;5:40.
Background
Early-life exposure to household pets has the capacity to reduce risk for overweight and allergic disease, especially following caesarean delivery. Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health. To investigate the impact of pre- and postnatal pet exposure on infant gut microbiota following various birth scenarios, this study employed a large subsample of 746 infants from the Canadian Healthy Infant Longitudinal Development Study (CHILD) cohort, whose mothers were enrolled during pregnancy between 2009 and 2012. Participating mothers were asked to report on household pet ownership at recruitment during the second or third trimester and 3 months postpartum. Infant gut microbiota were profiled with 16S rRNA sequencing from faecal samples collected at the mean age of 3.3 months. Two categories of pet exposure (i) only during pregnancy and (ii) pre- and postnatally were compared to no pet exposure under different birth scenarios.
Results
Over half of studied infants were exposed to at least one furry pet in the prenatal and/or postnatal periods, of which 8% were exposed in pregnancy alone and 46.8% had exposure during both time periods. As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P < 0.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P < 0.001, FDRp = 0.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06–0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16–0.58) for exposure in the pre- and postnatal time periods. All of these associations were independent of maternal asthma/allergy status, siblingship, breastfeeding exclusivity and other home characteristics.
Conclusions
The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity.
Electronic supplementary material
The online version of this article (doi:10.1186/s40168-017-0254-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s40168-017-0254-x
PMCID: PMC5382463  PMID: 28381231
Pets; Infant gut microbiota; Birth; Prenatal; Postnatal
11.  Ethnic and diet-related differences in the healthy infant microbiome 
Genome Medicine  2017;9:32.
Background
The infant gut is rapidly colonized by microorganisms soon after birth, and the composition of the microbiota is dynamic in the first year of life. Although a stable microbiome may not be established until 1 to 3 years after birth, the infant gut microbiota appears to be an important predictor of health outcomes in later life.
Methods
We obtained stool at one year of age from 173 white Caucasian and 182 South Asian infants from two Canadian birth cohorts to gain insight into how maternal and early infancy exposures influence the development of the gut microbiota. We investigated whether the infant gut microbiota differed by ethnicity (referring to groups of people who have certain racial, cultural, religious, or other traits in common) and by breastfeeding status, while accounting for variations in maternal and infant exposures (such as maternal antibiotic use, gestational diabetes, vegetarianism, infant milk diet, time of introduction of solid food, infant birth weight, and weight gain in the first year).
Results
We demonstrate that ethnicity and infant feeding practices independently influence the infant gut microbiome at 1 year, and that ethnic differences can be mapped to alpha diversity as well as a higher abundance of lactic acid bacteria in South Asians and a higher abundance of genera within the order Clostridiales in white Caucasians.
Conclusions
The infant gut microbiome is influenced by ethnicity and breastfeeding in the first year of life. Ethnic differences in the gut microbiome may reflect maternal/infant dietary differences and whether these differences are associated with future cardiometabolic outcomes can only be determined after prospective follow-up.
Electronic supplementary material
The online version of this article (doi:10.1186/s13073-017-0421-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13073-017-0421-5
PMCID: PMC5372248  PMID: 28356137
Infant gut microbiome; Ethnicity; Breastfeeding; Diet
12.  Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function 
The Journal of Clinical Investigation  null;126(11):4303-4318.
Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release–activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel–deficient patients and mice with ectodermal tissue–specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.
doi:10.1172/JCI89056
PMCID: PMC5096923  PMID: 27721237
13.  Asthma and the microbiome: defining the critical window in early life 
Asthma is a chronic inflammatory immune disorder of the airways affecting one in ten children in westernized countries. The geographical disparity combined with a generational rise in prevalence, emphasizes that changing environmental exposures play a significant role in the etiology of this disease. The microflora hypothesis suggests that early life exposures are disrupting the composition of the microbiota and consequently, promoting immune dysregulation in the form of hypersensitivity disorders. Animal model research supports a role of the microbiota in asthma and atopic disease development. Further, these model systems have identified an early life critical window, during which gut microbial dysbiosis is most influential in promoting hypersensitivity disorders. Until recently this critical window had not been characterized in humans, but now studies suggest that the ideal time to use microbes as preventative treatments or diagnostics for asthma in humans is within the first 100 days of life. This review outlines the major mouse-model and human studies leading to characterization of the early life critical window, emphasizing studies analyzing the intestinal and airway microbiotas in asthma and atopic disease. This research has promising future implications regarding childhood immune health, as ultimately it may be possible to therapeutically administer specific microbes in early life to prevent the development of asthma in children.
doi:10.1186/s13223-016-0173-6
PMCID: PMC5217603  PMID: 28077947
Microbiota; Asthma; Early life; Critical window; Hygiene hypothesis; Microflora hypothesis
14.  Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4 Months: Differences in Relative versus Absolute Concentrations 
Our gut microbiota provide a number of important functions, one of which is the metabolism of dietary fiber and other macronutrients that are undigested by the host. The main products of this fermentation process are short-chain fatty acids (SCFAs) and other intermediate metabolites including lactate and succinate. Production of these metabolites is dependent on diet and gut microbiota composition. There is increasing evidence for the role of SCFAs in host physiology and metabolic processes as well as chronic inflammatory conditions such as allergic disease and obesity. We aimed to investigate differences in fecal SCFAs and intermediate metabolites in 163 infants at 3–5 months of age according to breastfeeding status. Compared to no exposure to human milk at time of fecal sample collection, exclusive breastfeeding was associated with lower absolute concentrations of total SCFAs, acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate, yet higher concentrations of lactate. Further, the relative proportion of acetate was higher with exclusive breastfeeding. Compared to non-breastfed infants, those exclusively breastfed were four times more likely (aOR 4.50, 95% CI 1.58–12.82) to have a higher proportion of acetate relative to other SCFAs in their gut. This association was independent of birth mode, intrapartum antibiotics, infant sex, age, recruitment site, and maternal BMI or socioeconomic status. Our study confirms that breastfeeding strongly influences the composition of fecal microbial metabolites in infancy.
doi:10.3389/fnut.2017.00011
PMCID: PMC5385454
short-chain fatty acids; lactate; succinate; breastfeeding; infants; gut microbiota
15.  AllerGen’s 8th research conference 
Arrieta, Marie-Claire | Arevalos, Andrea | Stiemsma, Leah | Chico, Marta E. | Sandoval, Carlos | Jin, Minglian | Walter, Jens | Cooper, Phil | Finlay, Brett | Bernatchez, Emilie | Gold, Matthew J. | Langlois, Anick | Blais-Lecours, Pascale | Duchaine, Caroline | Marsolais, David | McNagny, Kelly M. | Blanchet, Marie-Renée | Brubacher, Jordan | Chhetri, Bimal | Sabaliauskas, Kelly | Bassil, Kate | Kwong, Jeff | Coates, Frances | Takaro, Tim K. | Chow, Angela | Miller, Gregory E. | Chen, Edith | Mandhane, Piushkumar J. | Turvey, Stuart E. | Elliott, Susan J. | Becker, Allan B. | Subbarao, Padmaja | Sears, Malcolm R. | Kozyrskyj, Anita L. | Dubeau, Aimée | Lu, Zihang | Balkovec, Susan | Kowalik, Krzysztof | Gustafsson, Per | Ratjen, Felix | Edgar, Rachel D. | Bush, Nicole R. | MacIssac, Julie L. | McEwen, Lisa M. | Boyce, Thomas W. | Kobor, Michael S. | Emmerson, Melanie | Dubeau, Aimée | Lu, Zihang | Shen, Bingqing | Kowalik, Krzysztof | Ratjen, Felix | Moraes, Theo J. | Gabrielli, Sofianne | Clarke, Ann | Eisman, Harley | Morris, Judy | Joseph, Lawrence | LaVieille, Sebastien | Ben-Shoshan, Moshe | Islam, Sumaiya A. | Brückmann, Christof | Nieratschker, Vanessa | Jamieson, Kyla C. | Proud, David | Kanagaratham, Cynthia | Camateros, Pierre | Kopriva, Frantisek | Henri, Jennifer | Hajduch, Marian | Radzioch, Danuta | Kang, Liane J. | Koleva, Petya T. | Field, Catherine J. | Konya, Tedd | Scott, James A. | Konya, Theodore | Azad, Meghan B. | Brook, Jeff | Guttman, David | Kumari, Manjeet | Bridgman, Sarah L. | Tun, Mon H. | Mandal, Rupasri | Wishart, David S. | Lee, Amy H. Y. | Xia, Jeff | Gill, Erin | Hancock, Bob | Maestre, Danay | Sutherland, Darren | Hirota, Jeremy | Pena, Olga | Carlsten, Christopher | McEwen, Lisa M. | Jones, Meaghan J. | MacIsaac, Julia L. | Dow, William H. | Rosero-Bixby, Luis | Rehkopf, David H. | Morimoto, Takeshi | Smith, Steven G. | Oliveria, John-Paul | Beaudin, Suzanne | Schlatman, Abbey | Howie, Karen | Obminski, Caitlin | Nusca, Graeme | Sehmi, Roma | Gauvreau, Gail M. | O’Byrne, Paul M. | North, Michelle | Peng, Cheng | Sanchez-Guerra, Marco | Byun, Hyang-Min | Ellis, Anne K. | Baccarelli, Andrea A. | Okeme, Joseph O. | Dhal, Suman | Saini, Aman | Diamond, Miriam L. | Olesovsky, Christopher J. | Salter, Brittany M. | Wang, Michael | Lacy, Paige | O’Sullivan, Michael J. | Park, Chan Y. | Fredberg, Jeffrey J. | Lauzon, Anne-Marie | Martin, James G. | Ryu, Min Hyung | Mookherjee, Neeloffer | Carlsten, Christopher | Simons, Elinor | Lefebvre, Diana | Dai, David | Singh, Amrit | Shannon, Casey P. | Kim, Young Woong | Yang, Chen Xi | Mark FitzGerald, J. | Boulet, Louis-Philippe | Tebbutt, Scott J. | Singhera, Gurpreet K. | JasemineYang, S. | Dorscheid, Delbert R. | Sinnock, Hasantha | Goruk, Susan | Tavakoli, Hamid | Lynd, Larry D. | Sadatsafavi, Mohsen | Tenn, Mark W. | Thiele, Jenny | Adams, Daniel E. | Steacy, Lisa M. | Ellis, Anne K. | Torabi, Bahar | De Schryver, Sarah | Lejtenyi, Duncan | Baerg, Ingrid | Chan, Edmond S. | Mazer, Bruce D. | Tran, Maxwell M. | Dai, Wei Hao | Lou, Wendy | Chari, Radha S. | Conway, Edward M. | Neighbour, Helen | Larché, Mark | Tebbutt, Scott J
doi:10.1186/s13223-016-0164-7
PMCID: PMC5260783
16.  Assessment of Genetic Associations between Common Single Nucleotide Polymorphisms in RIG-I-Like Receptor and IL-4 Signaling Genes and Severe Respiratory Syncytial Virus Infection in Children: A Candidate Gene Case-Control Study 
PLoS ONE  2014;9(6):e100269.
The majority of cases of severe pediatric respiratory syncytial virus (RSV) infection occur in otherwise healthy infants who have no identifiable risk factors, suggesting that additional subclinical factors, such as population genetic variation, influence the course of RSV infection. The objective of this study was to test if common single nucleotide polymorphisms (SNPs) in genes encoding for immune signalling components of the RIG-I-like receptor (RLR) and IL-4-signalling pathways affect the outcome of RSV infection in early life. We genotyped 8 SNPs using allele-specific probes combined with real-time PCR. Each of the SNPs tested had previously been established to have a functional impact on immune responsiveness and two of the SNPs in the IL4 and IL4R genes had previously been associated with severe RSV bronchiolitis. Association with susceptibility to severe RSV infection was tested by statistically comparing genotype and allele frequencies in infants and young children hospitalized with severe RSV bronchiolitis (n = 140) with two control groups—children who tested positive for RSV but did not require hospitalization (n = 100), and a general population control group (n = 285). Our study was designed with sufficient power (>80%) to detect clinically-relevant associations with effect sizes ≥1.5. However, we detected no statistically significant differences in allele and genotype frequencies of the investigated SNPs between the inpatient and control groups. To conclude, we could not replicate the previously reported association with SNPs in the IL4 and IL4R genes in our independent cohort, nor did we find that common SNPs in genes encoding for RLRs and the downstream adapter MAVS were associated with susceptibility to severe RSV infections. Despite the existing evidence demonstrating a functional immunological impact of these SNPs, our data suggest that the biological effect of each individual SNP is unlikely to affect clinical outcomes of RSV infection.
doi:10.1371/journal.pone.0100269
PMCID: PMC4064989  PMID: 24949794
17.  Pathogen recognition receptors crosstalk in respiratory syncytial virus sensing: host and cell type perspective 
Trends in microbiology  2013;21(11):568-574.
Human respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in young children, immunocompromized adults and the elderly. The innate immune response plays a pivotal role in host defense against RSV, but whether severe outcomes following RSV infection result from excessive or poor innate immune recognition remains unclear. Recent research suggests a situation in which crosstalk between families of pattern recognition receptors (PRRs) occurs in a cell type-dependent manner. The current challenge to empower novel therapeutic approaches and vaccine development is to confirm the role of the individual receptors in RSV pathogenesis in humans.
doi:10.1016/j.tim.2013.08.006
PMCID: PMC4848032  PMID: 24119913 CAMSID: cams4628
Respiratory Syncytial Virus; Pathogen Recognition Receptors; Innate immunity; Pathogenesis
18.  Cognitive Enhancement in Infants Associated with Increased Maternal Fruit Intake During Pregnancy: Results from a Birth Cohort Study with Validation in an Animal Model☆ 
EBioMedicine  2016;8:331-340.
In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37; p < 0.05). Consistent with this, we found 30% higher learning Performance index (PI) scores in Drosophila offspring from parents who consumed 30% fruit juice supplementation prenatally (PI: 85.7; SE 1.8; p < 0.05) compared to the offspring of standard diet parents (PI: 65.0 SE 3.4). Using the Drosophila model, we also show that the cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect, as prenatal fruit associated cognitive enhancement was blocked in Drosophila rutabaga mutants with reduced Ca2 +-Calmodulin-dependent adenylyl cyclase. Moreover, gestation is a critical time for this effect as postnatal fruit intake did not enhance cognitive performance in either humans or Drosophila. Our study supports increased fruit consumption during pregnancy with significant increases in infant cognitive performance. Validation in Drosophila helps control for potential participant bias or unmeasured confounders.
Graphical Abstract
Image 1
Highlights
•Gestational fruit intake positively correlates with infant cognitive performance.•Similar findings in a birth cohort and in Drosophila learning and memory scores•Cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect.•Postnatal fruit intake did not enhance cognitive outcomes in humans or Drosophila.
Fruits have been an important part of the human diet for thousands of years. We wanted to know if more fruit intake improves our ability to learn. Using data from the Canadian Healthy Infant Longitudinal Development (CHILD) study, we found that mothers who ate more fruit during pregnancy had children who did better on developmental testing at 1 year of age. Similarly, fruit flies had improved learning and memory if their parents had more fruit juice in their diet. In both humans and in the flies, there was no improvement in learning when only the babies were fed fruit.
doi:10.1016/j.ebiom.2016.04.025
PMCID: PMC4919537  PMID: 27428442
Gestational diet; Fruit; Birth cohort; Drosophila learning
19.  The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host 
Infection and Immunity  2015;83(7):2636-2650.
Bacterial pathogens produce a number of autotransporters that possess diverse functions. These include the family of serine protease autotransporters of Enterobacteriaceae (SPATEs) produced by enteric pathogens such as Shigella flexneri and enteroaggregative Escherichia coli. Of these SPATEs, one termed “protein involved in colonization,” or Pic, has been shown to possess mucinase activity in vitro, but to date, its role in in vivo enteric pathogenesis is unknown. Testing a pic null (ΔpicC) mutant in Citrobacter rodentium, a natural mouse pathogen, found that the C. rodentium ΔpicC strain was impaired in its ability to degrade mucin in vitro compared to the wild type. Upon infection of mice, the ΔpicC mutant exhibited a hypervirulent phenotype with dramatically heavier pathogen burdens found in intestinal crypts. ΔpicC mutant-infected mice suffered greater barrier disruption and more severe colitis and weight loss, necessitating their euthanization between 10 and 14 days postinfection. Notably, the virulence of the ΔpicC mutant was normalized when the picC gene was restored; however, a PicC point mutant causing loss of mucinase activity did not replicate the ΔpicC phenotype. Exploring other aspects of PicC function, the ΔpicC mutant was found to aggregate to higher levels in vivo than wild-type C. rodentium. Moreover, unlike the wild type, the C. rodentium ΔpicC mutant had a red, dry, and rough (RDAR) morphology in vitro and showed increased activation of the innate receptor Toll-like receptor 2 (TLR2). Interestingly, the C. rodentium ΔpicC mutant caused a degree of pathology similar to that of wild-type C. rodentium when infecting TLR2-deficient mice, showing that despite its mucinase activity, PicC's major role in vivo may be to limit C. rodentium's stimulation of the host's innate immune system.
doi:10.1128/IAI.00025-15
PMCID: PMC4468532  PMID: 25895966
20.  Dual Proteolytic Pathways Govern Glycolysis and Immune Competence 
Cell  2014;159(7):1578-1590.
SUMMARY
Proteasomes and lysosomes constitute the major cellular systems that catabolize proteins to recycle free amino acids for energy and new protein synthesis. Tripeptidyl peptidase II (TPPII) is a large cytosolic proteolytic complex that functions in tandem with the proteasome-ubiquitin protein degradation pathway. We found that autosomal recessive TPP2 mutations cause recurrent infections, autoimmunity, and neurodevelopmental delay in humans. We show that a major function of TPPII in mammalian cells is to maintain amino acid levels, and that TPPII-deficient cells compensate by increasing lysosome number and proteolytic activity. However, the overabundant lysosomes derange cellular metabolism by consuming the key glycolytic enzyme hexokinase-2 through chaperone-mediated autophagy. This reduces glycolysis and impairs the production of effector cytokines including IFN-γ and IL-1β. Thus, TPPII controls the balance between intracellular amino acid availability, lysosome number, and glycolysis, which is vital for adaptive and innate immunity and neurodevelopmental health.
doi:10.1016/j.cell.2014.12.001
PMCID: PMC4297473  PMID: 25525876
21.  The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling 
Nature Communications  2015;6:8777.
Antigen receptor signalling activates the canonical NF-κB pathway via the CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined roles for linear ubiquitination. The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in NF-κB activation and in B-cell lymphoma subtypes. To identify new human MALT1 substrates, we compare B cells from the only known living MALT1mut/mut patient with healthy MALT1+/mut family members using 10-plex Tandem Mass Tag TAILS N-terminal peptide proteomics. We identify HOIL1 of the linear ubiquitin chain assembly complex as a novel MALT1 substrate. We show linear ubiquitination at B-cell receptor microclusters and signalosomes. Late in the NF-κB activation cycle HOIL1 cleavage transiently reduces linear ubiquitination, including of NEMO and RIP1, dampening NF-κB activation and preventing reactivation. By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regulator of the human canonical NF-κB pathway—first promoting activation via the CBM—then triggering HOIL1-dependent negative-feedback termination, preventing reactivation.
MALT1 mediates NFκB activation. Here the authors perform proteomic analysis of human immunodeficient mutant MALT1 B cells revealing that MALT1 cleaves the HOIL1 subunit of the linear ubiquitin chain assembly complex to dampen late NFκB activation and to invoke negative feedback of NFκB activation.
doi:10.1038/ncomms9777
PMCID: PMC4659944  PMID: 26525107
22.  Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients 
Type 1A diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration of the pancreatic islets of Langerhans. A major impediment to advances in understanding, preventing, and curing T1D has been the inability to “see” the disease initiate, progress, or regress, especially during the occult phase. Here, we report the development of a noninvasive method to visualize T1D at the target organ level in patients with active insulitis. Specifically, we visualized islet inflammation, manifest by microvascular changes and monocyte/macrophage recruitment and activation, using magnetic resonance imaging of magnetic nanoparticles (MNPs). As a proof of principle for this approach, imaging of infused ferumoxtran-10 nanoparticles permitted effective visualization of the pancreas and distinction of recent-onset diabetes patients from nondiabetic controls. The observation that MNPs accumulate in the pancreas of T1D patients opens the door to exploiting this noninvasive imaging method to follow T1D progression and monitoring the ability of immunomodulatory agents to clear insulitis.
doi:10.1172/JCI44339
PMCID: PMC3007157  PMID: 21123946
23.  Impaired NLRP3 inflammasome activity during fetal development regulates IL-1β production in human monocytes 
European journal of immunology  2014;45(1):238-249.
Interleukin-1β (IL-1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed the extent of variability within the Toll-like receptor (TLR)/NLRP3 inflammasome pathways in human neonates. We show that immature low CD14-expressing/CD16pos monocytes predominate before 33 weeks of gestation, and that these cells lack production of the pro-IL-1β precursor protein upon LPS stimulation. In contrast, high levels of pro-IL-1β are produced within high CD14-expressing monocytes, although they are unable to secrete mature IL-1β. The lack of secreted IL-1β in these monocytes parallels a reduction of TLR-mediated NLRP3 induction resulting in a lack of caspase-1 activity before 29 weeks of gestation, whereas expression of the ASC protein and function of the P2X7 receptor are preserved. Our analyses also reveal a strong inhibitory effect of placental infection on LPS/ATP-induced caspase-1 activity in cord blood monocytes. Lastly, secretion of IL-1β in preterm neonates is restored to adult levels during the neonatal period, indicating rapid maturation of these responses after birth. Collectively, our data highlight important developmental mechanisms regulating IL-1β responses early in gestation, in part due to a downregulation of TLR-mediated NLRP3 expression. Such mechanisms may serve to limit potentially damaging inflammatory responses in a developing fetus.
doi:10.1002/eji.201444707
PMCID: PMC4619041  PMID: 25311115 CAMSID: cams5029
Neonate; Interleukin-1 beta (IL-1β); Inflammasome; Toll-like receptor; Human
24.  The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures 
The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3–4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set.
doi:10.1038/jes.2015.7
PMCID: PMC4611361  PMID: 25805254
environmental exposure assessment; longitudinal birth cohort; indoor air quality; etiology of asthma; biomarkers; CHILD study
25.  Hierarchical maturation of innate immune defences in very preterm neonates 
Neonatology  2014;106(1):1-9.
Background
Preterm neonates are highly vulnerable to infection.
Objectives
To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses.
Methods
Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists: TLR4 (LPS), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term.
Results
TLR responses develop asynchronously in preterm neonates, whereas responses to TLR7/8 were more mature and followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses.
Conclusions
The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.
doi:10.1159/000358550
PMCID: PMC4556450  PMID: 24603545 CAMSID: cams5026
Neonate; infection; Toll-like receptor; antenatal corticosteroids; chorioamnionitis

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