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Is the Prevalence of Peanut Allergy Increasing? A Five-year Follow-up Study on the Prevalence of Peanut Allergy in Montreal School Children Aged 5 to 9 Years
Abstracts S97
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
374
Development of an Algorithm to Better Predict Clinical Responsiveness to Peanut A. K. Marrin1, K. Sun1, M. Jordana1, G. Foster1, C. Goldsmith1, F. E. Simons2, K. T. HayGlass2, S. Waserman1; 1McMaster University, Hamilton, ON, CANADA, 2University of Manitoba, Winnipeg, MB, CANADA. RATIONALE: Children at risk of peanut allergy often avoid peanut, yet a subgroup shows sensitization to peanut on skin prick tests (SPT) and serum specific IgE. Frequently, they must undergo an oral challenge to determine if they are truly allergic. This study examines the relationship between SPT, peanut specific serum IgE, and cytokine production by peripheral blood mononuclear cells (PBMC) to generate an algorithm to better predict peanut allergy. METHODS: Patient groups: 1) True positives: History of peanut allergy and a positive peanut SPT. 2) False positives: Tolerate peanut but have a positive peanut SPT. 3) Unknown reactivity: Positive peanut SPT but no previous peanut ingestion 4) Non-atopic controls. PBMCs were isolated and cultured in the presence and absence of peanut. Cytokines were measured at baseline and in the presence of peanut. Statistical analysis was done using Classification And Regression Trees (CART). RESULTS: Peanut specific IgE levels ranged from 0 to >100 kU/L in peanut allergic patients and patients with unknown reactivity. False positive individuals had IgE levels from 0 to 27 kU/L. Non-atopic controls had undetectable peanut specific IgE. Of 12 variables examined, 4 variables identified as important for predicting peanut reactivity by CART analysis were wheal size, patient age, total IgE, and IFN-Gamma. CONCLUSIONS: In peanut allergic individuals, there is significant variability in peanut specific IgE. CART analysis identified 4 variables as important for predicting peanut reactivity. The next phase involves validation of the algorithm through oral peanut challenge in patients with unknown reactivity. Funding: Food Allergy Initiative
375
Is the Prevalence of Peanut Allergy Increasing? A Five-year Follow-up Study on the Prevalence of Peanut Allergy in Montreal School Children Aged 5 to 9 Years M. Ben-Shoshan1, R. S. Kagan1, R. Alizadehfar1, L. Joseph2, E. Turnbull3, Y. St. Pierre3, A. E. Clarke4; 1Department of Pediatrics, Division of Clinical Immunology/Allergy and Rheumatology, McGill University Health Center, Montreal, QC, CANADA, 2Department of Medicine, Division of Clinical Epidemiology, McGill University Health Center AND Departments of Epidemiology and Biostatistics, McGill University, Montreal, QC, CANADA, 3Department of Medicine, Division of Clinical Epidemiology, McGill University Health Center, Montreal, QC, CANADA, 4Department of Medicine, Division of Clinical Epidemiology, McGill University Health Center AND Department of Medicine, Division of Clinical Immunology/Allergy, McGill University Health Center, Montreal, QC, CANADA. RATIONALE: To determine if peanut allergy prevalence in Montreal is increasing. METHODS: Questionnaires regarding peanut ingestion were administered to parents of children in randomly selected kindergarten through grade 3 classrooms in both 2000/2002 and 2005/2007. Respondents were stratified as: 1) peanut tolerant, 2) never/rarely ingest peanut, 3) convincing history of peanut allergy, or 4) uncertain history of peanut allergy. Groups 2, 3 and 4 required skin prick tests (SPTs). Children in Group 3 with positive SPTs were considered peanut-allergic. Children in Groups 2 and 4 with positive SPTs had peanut-specific IgE measured and if < 15 kUA/L, an oral peanut challenge. To generate prevalence estimates which incorporated respondents providing incomplete data and non-respondents, multiple imputation was used.
RESULTS: Of 7546 children surveyed in 2005/2007, 4855 responded, 93% in Group 1. Among those providing complete data, the prevalence was 1.71% (95% CI, 1.36%, 2.13%) in 2005/2007 versus 1.50% (95% CI, 1.16%, 1.92%) in 2000/2002. After adjustment for missing data, the prevalence was 1.81% (95% CI, 1.50%, 2.16%) in 2005/2007 versus 1.34% (95% CI, 1.08%, 1.64%) in 2000/2002. The differences between the prevalence in 2005/2007 and 2000/2002 were 0.21% (95% CI, -0.31%, 0.73%) among those providing complete data and 0.47% (95% CI, 0.05%, 0.89%) after adjustment for missing data. CONCLUSIONS: This is the first North American study to document temporal trends in peanut allergy prevalence by corroborating history with confirmatory tests. The results suggest an increase in prevalence of approximately 35% in five years. However, our wide CIs preclude definitive conclusions. Funding: AllerGen, Canadian Institutes of Health Research, Fonds de la recherche en sante´ du Que´bec, Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, Health Canada, Novartis Pharmaceutial
376
Diacylglycerol Kinase Deficiency Increases the Peanut Allergic Response in Mice X. Zhong, M. Kulis, R. Guo, L. Pons, A. W. Burks; Duke University, Durham, NC. RATIONALE: Diacylglycerol kinase zeta (DGKz) negatively regulates TCR signaling and T cell activation, while positively regulating IL-12 production and TLR signaling. We hypothesized that DGKz -/- mice would develop elevated peanut allergic responses compared with their wild-type counterparts, C57/BL6. METHODS: Age-matched female DGKz -/- and wild-type mice were sensitized to peanut by i.p. injection with alum. The allergic state was assessed by i.p. challenge with peanut with subsequent monitoring of anaphylactic symptoms, core body temperature, and mouse mast cell protease-1 (MMCP-1) levels in the serum. Peanut-specific IgE and IgG1 were quantified by ELISA. RESULTS: Anaphylactic symptom scores were significantly increased in DGKz -/- compared to wild-type mice (median score 5 4 and 0.5, respectively; p < 0.05), as was the change in body temperature (mean 5 -8.3 and -3.5, respectively; p < 0.01). MMCP-1 was elevated in DGKz -/- mice following challenge. The differences in in vivo response is likely the result of increased anaphylactic antibodies to peanut; mean IgE: 365.7 ng/ml for DGKz -/- and 225.6 ng/ml for wild-type (p < 0.01) and mean IgG1: 159.7 ug/ml for DGKz -/- and 77.1 ug/ml for wild-type (p < 0.05). CONCLUSIONS: DGKz has a protective role in the development of peanut hypersensitivity, as DGKz deficient mice develop significantly higher peanut-specific IgE and in vivo reactions to peanut. The immunological compartments responsible for protection will be systematically studied in these mice to aid in the understanding of peanut sensitization mechanisms in humans. Funding: Food Allergy Project
SUNDAY
solution. Results demonstrate that oral tolerance can be facilitated through simple methods, possibly by altering solubility or digestibility of food proteins. (This abstract does not reflect EPA policy.) Funding: Environmental Protection Agency
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
374
Development of an Algorithm to Better Predict Clinical Responsiveness to Peanut A. K. Marrin1, K. Sun1, M. Jordana1, G. Foster1, C. Goldsmith1, F. E. Simons2, K. T. HayGlass2, S. Waserman1; 1McMaster University, Hamilton, ON, CANADA, 2University of Manitoba, Winnipeg, MB, CANADA. RATIONALE: Children at risk of peanut allergy often avoid peanut, yet a subgroup shows sensitization to peanut on skin prick tests (SPT) and serum specific IgE. Frequently, they must undergo an oral challenge to determine if they are truly allergic. This study examines the relationship between SPT, peanut specific serum IgE, and cytokine production by peripheral blood mononuclear cells (PBMC) to generate an algorithm to better predict peanut allergy. METHODS: Patient groups: 1) True positives: History of peanut allergy and a positive peanut SPT. 2) False positives: Tolerate peanut but have a positive peanut SPT. 3) Unknown reactivity: Positive peanut SPT but no previous peanut ingestion 4) Non-atopic controls. PBMCs were isolated and cultured in the presence and absence of peanut. Cytokines were measured at baseline and in the presence of peanut. Statistical analysis was done using Classification And Regression Trees (CART). RESULTS: Peanut specific IgE levels ranged from 0 to >100 kU/L in peanut allergic patients and patients with unknown reactivity. False positive individuals had IgE levels from 0 to 27 kU/L. Non-atopic controls had undetectable peanut specific IgE. Of 12 variables examined, 4 variables identified as important for predicting peanut reactivity by CART analysis were wheal size, patient age, total IgE, and IFN-Gamma. CONCLUSIONS: In peanut allergic individuals, there is significant variability in peanut specific IgE. CART analysis identified 4 variables as important for predicting peanut reactivity. The next phase involves validation of the algorithm through oral peanut challenge in patients with unknown reactivity. Funding: Food Allergy Initiative
375
Is the Prevalence of Peanut Allergy Increasing? A Five-year Follow-up Study on the Prevalence of Peanut Allergy in Montreal School Children Aged 5 to 9 Years M. Ben-Shoshan1, R. S. Kagan1, R. Alizadehfar1, L. Joseph2, E. Turnbull3, Y. St. Pierre3, A. E. Clarke4; 1Department of Pediatrics, Division of Clinical Immunology/Allergy and Rheumatology, McGill University Health Center, Montreal, QC, CANADA, 2Department of Medicine, Division of Clinical Epidemiology, McGill University Health Center AND Departments of Epidemiology and Biostatistics, McGill University, Montreal, QC, CANADA, 3Department of Medicine, Division of Clinical Epidemiology, McGill University Health Center, Montreal, QC, CANADA, 4Department of Medicine, Division of Clinical Epidemiology, McGill University Health Center AND Department of Medicine, Division of Clinical Immunology/Allergy, McGill University Health Center, Montreal, QC, CANADA. RATIONALE: To determine if peanut allergy prevalence in Montreal is increasing. METHODS: Questionnaires regarding peanut ingestion were administered to parents of children in randomly selected kindergarten through grade 3 classrooms in both 2000/2002 and 2005/2007. Respondents were stratified as: 1) peanut tolerant, 2) never/rarely ingest peanut, 3) convincing history of peanut allergy, or 4) uncertain history of peanut allergy. Groups 2, 3 and 4 required skin prick tests (SPTs). Children in Group 3 with positive SPTs were considered peanut-allergic. Children in Groups 2 and 4 with positive SPTs had peanut-specific IgE measured and if < 15 kUA/L, an oral peanut challenge. To generate prevalence estimates which incorporated respondents providing incomplete data and non-respondents, multiple imputation was used.
RESULTS: Of 7546 children surveyed in 2005/2007, 4855 responded, 93% in Group 1. Among those providing complete data, the prevalence was 1.71% (95% CI, 1.36%, 2.13%) in 2005/2007 versus 1.50% (95% CI, 1.16%, 1.92%) in 2000/2002. After adjustment for missing data, the prevalence was 1.81% (95% CI, 1.50%, 2.16%) in 2005/2007 versus 1.34% (95% CI, 1.08%, 1.64%) in 2000/2002. The differences between the prevalence in 2005/2007 and 2000/2002 were 0.21% (95% CI, -0.31%, 0.73%) among those providing complete data and 0.47% (95% CI, 0.05%, 0.89%) after adjustment for missing data. CONCLUSIONS: This is the first North American study to document temporal trends in peanut allergy prevalence by corroborating history with confirmatory tests. The results suggest an increase in prevalence of approximately 35% in five years. However, our wide CIs preclude definitive conclusions. Funding: AllerGen, Canadian Institutes of Health Research, Fonds de la recherche en sante´ du Que´bec, Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, Health Canada, Novartis Pharmaceutial
376
Diacylglycerol Kinase Deficiency Increases the Peanut Allergic Response in Mice X. Zhong, M. Kulis, R. Guo, L. Pons, A. W. Burks; Duke University, Durham, NC. RATIONALE: Diacylglycerol kinase zeta (DGKz) negatively regulates TCR signaling and T cell activation, while positively regulating IL-12 production and TLR signaling. We hypothesized that DGKz -/- mice would develop elevated peanut allergic responses compared with their wild-type counterparts, C57/BL6. METHODS: Age-matched female DGKz -/- and wild-type mice were sensitized to peanut by i.p. injection with alum. The allergic state was assessed by i.p. challenge with peanut with subsequent monitoring of anaphylactic symptoms, core body temperature, and mouse mast cell protease-1 (MMCP-1) levels in the serum. Peanut-specific IgE and IgG1 were quantified by ELISA. RESULTS: Anaphylactic symptom scores were significantly increased in DGKz -/- compared to wild-type mice (median score 5 4 and 0.5, respectively; p < 0.05), as was the change in body temperature (mean 5 -8.3 and -3.5, respectively; p < 0.01). MMCP-1 was elevated in DGKz -/- mice following challenge. The differences in in vivo response is likely the result of increased anaphylactic antibodies to peanut; mean IgE: 365.7 ng/ml for DGKz -/- and 225.6 ng/ml for wild-type (p < 0.01) and mean IgG1: 159.7 ug/ml for DGKz -/- and 77.1 ug/ml for wild-type (p < 0.05). CONCLUSIONS: DGKz has a protective role in the development of peanut hypersensitivity, as DGKz deficient mice develop significantly higher peanut-specific IgE and in vivo reactions to peanut. The immunological compartments responsible for protection will be systematically studied in these mice to aid in the understanding of peanut sensitization mechanisms in humans. Funding: Food Allergy Project
SUNDAY
solution. Results demonstrate that oral tolerance can be facilitated through simple methods, possibly by altering solubility or digestibility of food proteins. (This abstract does not reflect EPA policy.) Funding: Environmental Protection Agency