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1.  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.
PMCID: PMC5390240
2.  Comparison of ImmunoCAP and Immulite serum specific IgE assays for the assessment of egg allergy 
Egg specific IgE levels are frequently used in combination with skin-prick tests to guide clinical decisions and to monitor egg allergy evolution in children. We compared both Immulite and ImmunoCAP egg specific IgE assays in egg allergic children, and found a linear correlation between both assays with a mean Immulite:ImmunoCAP ratio of 3. This is relevant information for clinicans wishing to estimate values from one assay to the other, as most literature has been published using the ImmunoCAP system.
PMCID: PMC4901419  PMID: 27293451
Egg allergy; Food allergy; Immulite; ImmunoCAP; UniCAP; Specific IgE assays
4.  Powder milk: a user-friendly and safe product for heated-milk food challenge? 
Previous studies have reported that up to 75 % of milk allergic subjects tolerate heated milk products. However, the food used for heated milk challenge is often prepared in a non-standardized manner by the parents at home, which may prove inconvenient and even sometimes raise concerns with regards to test validity. Instant skim milk powder is made by a food process that involves heating skim milk to up to 250 °C (390 °F) for up to 30 min which ought to be sufficient to denature thermo-labile proteins.
To appraise the use of instant skim milk for the purpose of heated milk food challenge.
We reviewed all oral food challenges to instant skim milk powder performed at Sainte-Justine University Hospital Center in Montreal, Canada between November 2008 and January 2013 (cumulative dose of 4 g proteins).
During the study period, 39 children underwent an open food challenge to instant skim milk powder. Thirty patients (76.9 %) passed the challenge without clinical reaction, of which 26 successfully introduced heated milk products at home. The remaining four children reported intermittent mild reactions to specific forms of heated milk goods while they tolerated others. Subjects’ clinical and paraclinical characteristics were comparable to previous cohorts evaluating baked milk challenge, which reported similar rates of heated milk positive challenges, ranging from 17 to 28 %.
Challenge with instant skim milk powder could be a safe, convenient and easily standardizable alternative to home baked food for heated milk challenge. Further controlled studies are needed before this can be implemented to practice.
PMCID: PMC4690356  PMID: 26705401
Heated milk; Baked milk; Milk allergy; Tolerance; Introduction; Powder milk; Challenge
5.  Human in vitro induced T regulatory cells and memory T cells share common demethylation of specific FOXP3 promoter region 
The FOXP3 gene is the master regulator for T regulatory cells and is under tight DNA methylation control at the Treg specific demethylated region (TSDR) in its first intron. This said, methylation of its promoter region, the significance of which is unknown, has also been associated with various immune-related disease states such as asthma, food allergy, auto-immunity and cancer. Here, we used induced T regulatory cells (iTreg) as a target cell population to identify candidate hypomethylated CpG sites in the FOXP3 gene promoter to design a DNA methylation quantitative assay for this region.
Three CpG sites at the promoter region showed clear demethylation pattern associated with high FOXP3 expression after activation in presence of TGFβ and were selected as primary targets to design methylation-dependent RT-PCR primers and probes. We then examined the methylation of this ‘inducible-promoter-demethylated-region’ (IPDR) in various FOXP3+ T cell subsets. Both naïve and memory thymic-derived Treg cells were found to be fully demethylated at both the IPDR and TSDR. Interestingly, in addition to iTregs, both CD25− and CD25lo conventional memory CD4+CD45RA− T cells displayed a high fraction of IPDR demethylated cells in absence of TSDR demethylation.
This implies that the fraction of memory T cells should be taken in account when interpreting FOXP3 promoter methylation results from clinical studies. This approach, which is available for testing in clinical samples could have diagnostic and prognostic value in patients with immune or auto-inflammatory diseases.
PMCID: PMC4617722  PMID: 26500760
Treg; Epigenetic; TSDR; FOXP3; Methylation; Promoter; Assay; IPDR; Induced
7.  Two year effects of food allergen immunotherapy on quality of life in caregivers of children with food allergies 
Food allergy (FA) can have serious psychosocial and economic repercussions on food-allergic children and their caregivers and be associated with negative effects on their quality of life. Food allergen immunotherapy (IT) is a promising experimental therapy but can be linked to anxiety. This study investigated the effects of IT on FA-specific health-related quality of life (HRQL) over a 24 month-follow-up in caregivers of children with single and multiple food allergies. We hypothesized that characteristics such as age, asthma at baseline and respiratory allergic reactions during therapy were key characteristics that influenced HRQL scores.
A validated Food Allergy Quality of Life – Parental Burden Questionnaire (FAQL-PB) was used to assess HRQL. It was randomly distributed to and filled out by caregivers of 57 food-allergic children enrolled in clinical trials of IT. The same parent answered the FABQL-PB questionnaire at baseline and for 6-month, 12- month, 18- month, and 24-month time points on IT.
Caregiver HRQL improved significantly (change < - 0.5, p <0.0001) at each follow-up time point compared to baseline. The percentages of caregivers with improvement in HRQL progressively increased (92% at 24 month-follow-up time point compared to baseline). HRQL improved more in caregivers of participants older than 10 years or desensitized to more than 4 food allergens than those who were not (p <0.0001). Caregivers of participants with pre-existing asthma or dose-related respiratory allergic reactions had less improvement in HRQL than those who did not (p <0.01).
IT lead to improvement in caregiver HRQL. Certain characteristics were associated with greater improvements in caregiver HRQL.
Electronic supplementary material
The online version of this article (doi:10.1186/1710-1492-10-57) contains supplementary material, which is available to authorized users.
PMCID: PMC4363059  PMID: 25788951
Food allergen immunotherapy; Food allergy; Quality of life; Health-related quality of life
8.  The Use of Epinephrine in Acute Allergic Reaction to Food 
Pediatric annals  2013;42(7):293-295.
PMCID: PMC4161447  PMID: 23805971
9.  Diagnosis of Food Allergy 
Pediatric annals  2013;42(6):102-109.
Diagnosis of food allergy can be challenging. Given the limited specificity of available allergy tests, these need to be interpreted in light of pre-test probability that is determined by a careful history. Using likelihood ratios calculated from previous publication may allow a more individualized assessment. This approach is likely to be most useful in patients with low to moderate results, below the 95% positive predictive value for that food. This review covers the diagnostic approach of immunoglobulin E-mediated food allergy. We first focus on the pre-test clinical assessment of a patient with a suspected food allergy. We then compare currently available diagnostic tests and discuss their performance for frequent food allergens. Finally, we conclude with the interpretation of allergy tests in light of the pre-test assessment to determine final probability of food allergy and indications for referral to an allergy specialist for food challenge.
PMCID: PMC4161456  PMID: 23718238
10.  Regulatory T cells and their roles in immune dysregulation and allergy 
Immunologic research  2014;58(0):358-368.
The main function of the immune system is to fight off potential infections, but also to maintain its activity below a level that would trigger self-reactivity. Regulatory T cells (Tregs) such as forkhead box P3+ (FOXP3) Tregs and type 1 regulatory T cells (Tr1) play an essential role in this active process, using several distinct suppressive mechanisms. A wide range of pathologies have been associated with altered Treg cell function. This is best exemplified by the impact of mutations of genes essential for Treg function and the associated autoimmune syndromes. This review summarizes the main features of different subtypes of Tregs and focuses on the clinical implications of their altered function in human studies. More specifically, we discuss abnormalities affecting FOXP3+ Tregs and Tr1 cells that will lead to autoimmune manifestations and/or allergic reactions, and the potential therapeutic use of Tregs.
PMCID: PMC4161462  PMID: 24781194
Regulatory T cells; Type 1 regulatory T cells; FOXP3; Allergy; Immune dysregulation
11.  Epigenetic regulation of asthma and allergic disease 
Epigenetics of asthma and allergic disease is a field that has expanded greatly in the last decade. Previously thought only in terms of cell differentiation, it is now evident the epigenetics regulate many processes. With T cell activation, commitment toward an allergic phenotype is tightly regulated by DNA methylation and histone modifications at the Th2 locus control region. When normal epigenetic control is disturbed, either experimentally or by environmental exposures, Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to daughter cells with cell replication but they can also be inherited through generations. In animal models, with constant environmental pressure, epigenetically determined phenotypes are amplified through generations and can last up to 2 generations after the environment is back to normal. In this review on the epigenetic regulation of asthma and allergic diseases we review basic epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then cover the transgenerational inheritance model of epigenetic traits and discuss how this could relate the amplification of asthma and allergic disease prevalence and severity through the last decades. Finally, we discuss recent epigenetic association studies for allergic phenotypes and related environmental risk factors as well as potential underlying mechanisms for these associations.
PMCID: PMC4057652  PMID: 24932182
Epigenetic; Asthma; Allergy; Atopy; Inheritance; Transgenerational; Methylation; Histone; Th2; Amplification hypothesis
12.  Multiple-allergen oral immunotherapy improves quality of life in caregivers of food-allergic pediatric subjects 
Food allergy (FA) negatively affects quality of life in caregivers of food-allergic children, imposing a psychosocial and economic burden. Oral immunotherapy (OIT) is a promising investigational therapy for FA. However, OIT can be a source of anxiety as it carries risk for allergic reactions. The effect of OIT with multiple food allergens (mOIT) on FA-specific health-related quality of life (HRQL) has never been studied in participants with multiple, severe food allergies. This study is the first to investigate the effects of mOIT on FA-related HRQL in caregivers of pediatric subjects.
Caregiver HRQL was assessed using a validated Food Allergy Quality of Life – Parental Burden (FAQL-PB) Questionnaire (J Allergy Clin Immunol 114(5):1159-1163, 2004). Parents of participants in two single-center Phase I clinical trials receiving mOIT (n = 29) or rush mOIT with anti-IgE (omalizumab) pre-treatment (n = 11) completed the FAQL-PB prior to study intervention and at 2 follow-up time-points (6 months and 18 months). Parents of subjects not receiving OIT (control group, n = 10) completed the FAQL-PB for the same time-points.
HRQL improved with clinical (change < -0.5) and statistical (p < 0.05) significance in the mOIT group (baseline mean 3.9, 95% CI 3.4-4.4; 6-month follow-up mean 2.5, 95% CI 2.0-3.0; 18-month follow-up mean 1.8, 95% CI 1.4-2.1) and rush mOIT group (baseline mean 3.9, 95% CI 3.1-4.7; 6-month follow-up mean 1.7, 95% CI 0.9-2.6; 18-month follow-up mean 1.3, 95% CI 0.3-2.4). HRQL scores did not significantly change in the control group (n = 10).
Multi-allergen OIT with or without omalizumab leads to improvement in caregiver HRQL, suggesting that mOIT can help relieve the psychosocial and economic burden FA imposes on caregivers of food-allergic children.
PMCID: PMC4032627  PMID: 24860608
Oral immunotherapy; Omalizumab; Anti-IgE; Food allergy; Oral desensitization; Quality of life; Health-related quality of life
14.  Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab 
Up to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein.
To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously.
Participants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries.
Twenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks.
These phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.
PMCID: PMC3936817  PMID: 24576338
Food allergy; Oral immunotherapy (OIT); Specific Oral Tolerance Induction (SOTI); Multiple food allergy; Safety; Efficacy; Omalizumab; Desensitization
15.  Safety and feasibility of oral immunotherapy to multiple allergens for food allergy 
Thirty percent of children with food allergy are allergic to more than one food. Previous studies on oral immunotherapy (OIT) for food allergy have focused on the administration of a single allergen at the time. This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time.
Participants underwent double-blind placebo-controlled food challenges (DBPCFC) up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. Reactions during dose escalations and home dosing were recorded in a symptom diary.
Forty participants met inclusion criteria on peanut DBPCFC. Of these, 15 were mono-allergic to peanut and 25 had additional food allergies. Rates of reaction per dose did not differ significantly between the two groups (median of 3.3% and 3.7% in multi and single OIT group, respectively; p = .31). In both groups, most reactions were mild but two severe reactions requiring epinephrine occurred in each group. Dose escalations progressed similarly in both groups although, per protocol design, those on multiple food took longer to reach equivalent doses per food (median +4 mo.; p < .0001).
Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT.
Trial registration NCT01490177
PMCID: PMC3913318  PMID: 24428859
Food allergy; Oral immunotherapy (OIT); Specific oral tolerance induction (SOTI); Multiple; Safety; Efficacy
18.  Transcription of Virulence Factors in Staphylococcus aureus Small-Colony Variants Isolated from Cystic Fibrosis Patients Is Influenced by SigB 
Journal of Bacteriology  2006;188(1):64-76.
Staphylococcus aureus small-colony variants (SCVs) are believed to account in part for the persistence of S. aureus during chronic infections. Little is understood about the gene expression profile that may explain the phenotype and distinguish SCVs from prototype S. aureus strains. In this study, DNA array transcriptional profiles of clinical SCVs isolated from the airways of cystic fibrosis patients were obtained and compared to those obtained from a laboratory-derived SCV strain (i.e., a respiratory-deficient hemB mutant) and prototype S. aureus strains. The genes commonly up-regulated in both hemB and clinical SCVs were found to be implicated in fermentation and glycolysis pathways. The well-known virulence regulator agr was not activated in SCVs, and such strains had low levels of alpha-toxin (hla) gene expression. Clinical SCVs also had a transcriptional signature of their own. Of striking interest is that many genes, most of them under the positive control of the alternate sigma factor SigB, were specifically up-regulated and differed in that way from that seen in prototype S. aureus and the hemB mutant. Since SigB influences up-regulation of adhesin type genes while indirectly down-regulating exoproteins and toxins, we evaluated the internalization and persistence of SCVs in mammalian cells. Results showed that clinical SCVs persisted much more efficiently in cells than the hemB and prototype strains and that a sigB mutant was a poor persister. Thus, it appears that the agr locus plays a minor role in the regulation of the virulon of SCVs, unlike SigB, which may have a key role in intracellular persistence.
PMCID: PMC1317593  PMID: 16352822

Results 1-18 (18)