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Predicting Food Challenge Outcomes for Baked Milk: Role of Specific IgE and Skin Prick Testing
79
Casein-specific Regulatory T Cells and Effector T Cells in Patients with Variable Milk Protein Tolerance J. D. Kattan, A. Nowak-We˛grzyn, M. Masilamani, A. O. Bhatt, H. A. Sampson; Mount Sinai School of Medicine, New York, NY. RATIONALE: About 75% of children with cow’s milk allergy tolerate baked milk (BM), and addition of BM to the diet appears to accelerate unheated milk tolerance. BM-reactive children have more severe milk allergy. We sought to examine the contribution of casein-specific regulatory T (Treg) cells and effector T cells to milk tolerance among milk allergic children. METHODS: We examined 92 subjects classified as BM-reactive (28), BM-tolerant (21 muffin-tolerant, 7 pizza-tolerant, 30 rice pudding-tolerant), or unheated milk-tolerant (6) based on oral food challenge (OFC). From blood obtained at the baseline OFC, PBMCs were cultured with purified caseins and controls for 7 days; proliferating Treg cells and effector T cells were identified by flow cytometry. Treg cells were defined as CD127-/CD25hi/FoxP3hi cells derived from CD3+/CD4+/CFSElo T cells. Effector T cells were defined as CD3+/CD4+/CFSElo T cells that were CD127+/-/CD25lo/FoxP3lo. Differences between clinical groups in Treg cell and effector T cell frequencies were analyzed using the Mann Whitney rank sum test. RESULTS: There was an upward trend in the Treg cell frequency from those who were BM-reactive (median 27.6%) to those who had outgrown their milk allergy (median 41.8%; P50.086), though differences were not significant between the 5 clinical groups. There were no significant differences in the median effector T cell frequencies between the groups. CONCLUSIONS: There was a higher frequency of casein-specific Treg cells in children with mild clinical disease. Further longitudinal studies examining the development of tolerance to less-baked products will elucidate the role that Treg cells and effector T cells play in this process.
80
Predicting Food Challenge Outcomes for Baked Milk: Role of Specific IgE and Skin Prick Testing L. M. Bartnikas, W. J. Sheehan, L. C. Schneider, W. Phipatanakul; Children’s Hospital Boston, Boston, MA. RATIONALE: Most children with cow’s milk allergy tolerate baked milk products, but little data exists on which children are candidates for baked milk challenge. We examined the correlation of specific IgE (sIgE) and skin prick testing (SPT) levels with baked milk challenge outcomes. METHODS: We performed a retrospective chart review of children who underwent baked milk challenges at Children’s Hospital Boston from September 2009 to August 2011. We evaluated SPT results, sIgE levels, demographics, and food challenge outcomes. RESULTS: 32 children underwent open challenges to baked milk and 26 (81%) passed. Of those who failed, 3 (50%) passed the initial clinic challenge but developed symptoms at home, days to months later. One child who ultimately failed at home required epinephrine. Compared to those who passed, children who failed were younger (median 8.52yrs and 3.69yrs, respectively; p50.01) and more likely to have eczema (50% and 100%, respectively; p50.01). Milk sIgE <1.1kU/L and casein sIgE <0.9kU/L each had a 90% negative predictive value (NPV). Milk wheal <13mm had a 90% NPV and all children who failed had a milk wheal _7mm. Casein wheal <9mm had a 95% NPV. > CONCLUSIONS: The majority of children allergic to cow’s milk tolerated baked milk. SPT and sIgE levels may be helpful in predicting outcomes of baked milk challenges. Interestingly, 50% of children who ultimately failed challenges developed symptoms to exposure at home, suggesting that the specific milk quantity and degree of heating in the baked product may allow passed food challenge outcome, but may not guarantee prolonged tolerance.
81
Reaction in the First Month of Life and a Lower Eliciting Dose are Risk Factors for Persistence of IgE-Mediated Cow's Milk Allergy A. Elizur1,2, N. Rajuan1, M. R. Goldberg1, M. Leshno3, A. Cohen1, Y. Katz1,2; 1Allergy and Immunology Institute, Asaf Harofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Zerifin, ISRAEL, 2 Department of Pediatrics, Asaf harofeh Medical Center, Zerifin, ISRAEL, 3Faculty of Management, Tel Aviv University, Tel Aviv, ISRAEL. RATIONALE: IgE-mediated cow’s milk allergy (IgE-CMA), albeit transient in most patients, persists in some infants beyond the first years of life. However, risk factors for persistence that could be applied to clinical care are not well described. METHODS: In a prospective population-based cohort study including 13,019 children followed from birth, 66 infants were diagnosed with IgECMA based on history, skin prick test (SPT) and an oral food challenge (OFC) when indicated. Infants with IgE-CMA were followed for 48-60 months. A telephone questionnaire regarding recent exposures to milk was performed every 6 months and recovery was evaluated by repeated OFC. Persistence was defined as IgE-CMA at the end of the study period. Patients’ atopic background, SPT results, and characteristics of reaction at initial exposure and during OFC were compared between infants with persistent IgE-CMA and those who recovered. Cox regression analysis was performed for multiple variables. RESULTS: Forty three infants (65.2%) recovered from IgE-CMA during the study period. Most infants (76.7%) recovered within the first 2 years. A reaction in the first 30 days of life (p50.026) and a reaction to an amount of milk of less than 10 ml on OFC (or on initial exposure if OFC was not performed) (p50.009) were found to be risk factors for persistence of IgECMA on multivariate analysis. CONCLUSIONS: Resolution occurs in most infants with IgE-CMA. Infants who react in the first month of life, or react to < 10 ml of milk are at increased risk for persistence. These parameters can be applied into clinical care.
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Role Of Egg-white-specific Iga And Iga2 Levels In Egg Allergy: A Longitudinal Cohort Study G. N. Konstantinou, A. Nowak-We˛grzyn, L. Bardina, S. H. Sicherer, H. Sampson; Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY. RATIONALE: Serum food-specific IgA antibodies have been associated with allergic symptoms mainly in cross-sectional, case-control studies. We sought to prospectively determine and compare egg-white-(EW)-specific IgA and IgA2 levels between EW-allergic children and children tolerating egg. METHODS: Nine children (8.562.6 years old) allergic to egg and all eggcontaining foods were followed prospectively until they became tolerant at least to foods containing baked-in egg. Serum samples from all patients were available at all follow-up time points. Four age-matched children (8.863.6 years old), with no previous history of egg allergy and with serum samples available from time points comparable to that of the study group, were used as controls. A specific, ultra-sensitive ELISA (range 0.39150ng/ml) was developed and utilized for EW-specific IgA and EWspecific-IgA2 determinations. RESULTS: EW-specific IgA2 levels increased significantly over a mean6SD time of 2.660.9 years in allergic children that became tolerant [median(IQR): 17.9(16.8) ng/ml vs 27(28.5) ng/ml, P50.021], but there was no significant change in EW-specific IgA [39.5(28.5) ng/ml vs 51.7(92.7) ng/ml, P50.173]. EW-specific IgA and EW-specific IgA2 in control subjects did not change over 2.360.7 years [EW-specific IgA 182.2(200) ng/ml vs 180.2(92.7) ng/ml, P50.273 and EW-specific IgA2 125(106.3) ng/ml vs 130(64.8) ng/ml, P50.465]. In addition, EW-specific IgA and IgA2 levels were significantly lower in egg-allergic patients compared with control subjects, (P<0.01). CONCLUSIONS: These results suggest a potential role for food-specific IgA, and in particular food-specific IgA2 antibodies, in the induction of food tolerance. Furthermore, this supports the potential role of immaturity or impairment of IgA production in the pathophysiology of food allergy.
SATURDAY
Abstracts AB21
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
Casein-specific Regulatory T Cells and Effector T Cells in Patients with Variable Milk Protein Tolerance J. D. Kattan, A. Nowak-We˛grzyn, M. Masilamani, A. O. Bhatt, H. A. Sampson; Mount Sinai School of Medicine, New York, NY. RATIONALE: About 75% of children with cow’s milk allergy tolerate baked milk (BM), and addition of BM to the diet appears to accelerate unheated milk tolerance. BM-reactive children have more severe milk allergy. We sought to examine the contribution of casein-specific regulatory T (Treg) cells and effector T cells to milk tolerance among milk allergic children. METHODS: We examined 92 subjects classified as BM-reactive (28), BM-tolerant (21 muffin-tolerant, 7 pizza-tolerant, 30 rice pudding-tolerant), or unheated milk-tolerant (6) based on oral food challenge (OFC). From blood obtained at the baseline OFC, PBMCs were cultured with purified caseins and controls for 7 days; proliferating Treg cells and effector T cells were identified by flow cytometry. Treg cells were defined as CD127-/CD25hi/FoxP3hi cells derived from CD3+/CD4+/CFSElo T cells. Effector T cells were defined as CD3+/CD4+/CFSElo T cells that were CD127+/-/CD25lo/FoxP3lo. Differences between clinical groups in Treg cell and effector T cell frequencies were analyzed using the Mann Whitney rank sum test. RESULTS: There was an upward trend in the Treg cell frequency from those who were BM-reactive (median 27.6%) to those who had outgrown their milk allergy (median 41.8%; P50.086), though differences were not significant between the 5 clinical groups. There were no significant differences in the median effector T cell frequencies between the groups. CONCLUSIONS: There was a higher frequency of casein-specific Treg cells in children with mild clinical disease. Further longitudinal studies examining the development of tolerance to less-baked products will elucidate the role that Treg cells and effector T cells play in this process.
80
Predicting Food Challenge Outcomes for Baked Milk: Role of Specific IgE and Skin Prick Testing L. M. Bartnikas, W. J. Sheehan, L. C. Schneider, W. Phipatanakul; Children’s Hospital Boston, Boston, MA. RATIONALE: Most children with cow’s milk allergy tolerate baked milk products, but little data exists on which children are candidates for baked milk challenge. We examined the correlation of specific IgE (sIgE) and skin prick testing (SPT) levels with baked milk challenge outcomes. METHODS: We performed a retrospective chart review of children who underwent baked milk challenges at Children’s Hospital Boston from September 2009 to August 2011. We evaluated SPT results, sIgE levels, demographics, and food challenge outcomes. RESULTS: 32 children underwent open challenges to baked milk and 26 (81%) passed. Of those who failed, 3 (50%) passed the initial clinic challenge but developed symptoms at home, days to months later. One child who ultimately failed at home required epinephrine. Compared to those who passed, children who failed were younger (median 8.52yrs and 3.69yrs, respectively; p50.01) and more likely to have eczema (50% and 100%, respectively; p50.01). Milk sIgE <1.1kU/L and casein sIgE <0.9kU/L each had a 90% negative predictive value (NPV). Milk wheal <13mm had a 90% NPV and all children who failed had a milk wheal _7mm. Casein wheal <9mm had a 95% NPV. > CONCLUSIONS: The majority of children allergic to cow’s milk tolerated baked milk. SPT and sIgE levels may be helpful in predicting outcomes of baked milk challenges. Interestingly, 50% of children who ultimately failed challenges developed symptoms to exposure at home, suggesting that the specific milk quantity and degree of heating in the baked product may allow passed food challenge outcome, but may not guarantee prolonged tolerance.
81
Reaction in the First Month of Life and a Lower Eliciting Dose are Risk Factors for Persistence of IgE-Mediated Cow's Milk Allergy A. Elizur1,2, N. Rajuan1, M. R. Goldberg1, M. Leshno3, A. Cohen1, Y. Katz1,2; 1Allergy and Immunology Institute, Asaf Harofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Zerifin, ISRAEL, 2 Department of Pediatrics, Asaf harofeh Medical Center, Zerifin, ISRAEL, 3Faculty of Management, Tel Aviv University, Tel Aviv, ISRAEL. RATIONALE: IgE-mediated cow’s milk allergy (IgE-CMA), albeit transient in most patients, persists in some infants beyond the first years of life. However, risk factors for persistence that could be applied to clinical care are not well described. METHODS: In a prospective population-based cohort study including 13,019 children followed from birth, 66 infants were diagnosed with IgECMA based on history, skin prick test (SPT) and an oral food challenge (OFC) when indicated. Infants with IgE-CMA were followed for 48-60 months. A telephone questionnaire regarding recent exposures to milk was performed every 6 months and recovery was evaluated by repeated OFC. Persistence was defined as IgE-CMA at the end of the study period. Patients’ atopic background, SPT results, and characteristics of reaction at initial exposure and during OFC were compared between infants with persistent IgE-CMA and those who recovered. Cox regression analysis was performed for multiple variables. RESULTS: Forty three infants (65.2%) recovered from IgE-CMA during the study period. Most infants (76.7%) recovered within the first 2 years. A reaction in the first 30 days of life (p50.026) and a reaction to an amount of milk of less than 10 ml on OFC (or on initial exposure if OFC was not performed) (p50.009) were found to be risk factors for persistence of IgECMA on multivariate analysis. CONCLUSIONS: Resolution occurs in most infants with IgE-CMA. Infants who react in the first month of life, or react to < 10 ml of milk are at increased risk for persistence. These parameters can be applied into clinical care.
82
Role Of Egg-white-specific Iga And Iga2 Levels In Egg Allergy: A Longitudinal Cohort Study G. N. Konstantinou, A. Nowak-We˛grzyn, L. Bardina, S. H. Sicherer, H. Sampson; Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY. RATIONALE: Serum food-specific IgA antibodies have been associated with allergic symptoms mainly in cross-sectional, case-control studies. We sought to prospectively determine and compare egg-white-(EW)-specific IgA and IgA2 levels between EW-allergic children and children tolerating egg. METHODS: Nine children (8.562.6 years old) allergic to egg and all eggcontaining foods were followed prospectively until they became tolerant at least to foods containing baked-in egg. Serum samples from all patients were available at all follow-up time points. Four age-matched children (8.863.6 years old), with no previous history of egg allergy and with serum samples available from time points comparable to that of the study group, were used as controls. A specific, ultra-sensitive ELISA (range 0.39150ng/ml) was developed and utilized for EW-specific IgA and EWspecific-IgA2 determinations. RESULTS: EW-specific IgA2 levels increased significantly over a mean6SD time of 2.660.9 years in allergic children that became tolerant [median(IQR): 17.9(16.8) ng/ml vs 27(28.5) ng/ml, P50.021], but there was no significant change in EW-specific IgA [39.5(28.5) ng/ml vs 51.7(92.7) ng/ml, P50.173]. EW-specific IgA and EW-specific IgA2 in control subjects did not change over 2.360.7 years [EW-specific IgA 182.2(200) ng/ml vs 180.2(92.7) ng/ml, P50.273 and EW-specific IgA2 125(106.3) ng/ml vs 130(64.8) ng/ml, P50.465]. In addition, EW-specific IgA and IgA2 levels were significantly lower in egg-allergic patients compared with control subjects, (P<0.01). CONCLUSIONS: These results suggest a potential role for food-specific IgA, and in particular food-specific IgA2 antibodies, in the induction of food tolerance. Furthermore, this supports the potential role of immaturity or impairment of IgA production in the pathophysiology of food allergy.
SATURDAY
Abstracts AB21
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2