Relationship of Cytokine and Regulatory Gene Expression to the Outcomes of Milk and Egg Allergy in an Atopic Cohort (COFAR2)

Abstract

S A T U R D A Y 94 Relationship of Cytokine and Regulatory Gene Expression to the Outcomes of Milk and Egg Allergy in an Atopic Cohort (COFAR2) S. H. Sicherer, D. Stablein, R. A. Wood, A. W. Burks, A. H. Liu, S. M. Jones, D. M. Fleischer, L. Mayer, R. Lindblad, A. Grishin, H. A. SampsonConsortium of Food Allergy Research. Mt. Sinai School of Medicine, New York, NY, EMMES Corp., Rockville, MD, Johns Hopkins University School of Medicine, Baltimore, MD, Duke, Durham, NC, National Jewish Health, Denver, CO, University of Arkansas for Medical Sciences, Little Rock, AR. RATIONALE: To determine lymphocyte activation biomarkers associated with milk/egg allergy over time. METHODS: Children aged 3-15 months with likely milk/egg allergy and no diagnosed peanut allergywere followed at baseline, 6, 12 and 24months and categorized as egg/milk allergic or tolerant by predefined criteria. Mononuclear cell allergen stimulation screening for CD25, CISH, FOXP3, GATA3, IL-10, IL-4, IFN-gamma and TBET expression using casein and egg white as stimulants were performed at each of the time points. Repeated measures analyses with generalized linear modeling were constructed to determine if gene expression was predictive of the allergy state (allergic or tolerant). RESULTS: The number of children with a confirmed/convincing milk allergy and number tolerant in parentheses among those tested at baseline (n5492), 6 (n5432), 12 (n5420) and 24(n5367) months were: 237(105), 197(137), 197(163) and 145(190), respectively. The corresponding results for egg were: 139(23), 132(35), 129(55) and 99 (117), respectively. The significant (p < 0.05) predictors of allergy based upon current gene expression values were: increased IL4 expression (milk) and decreased GATA3 (egg). Considering change in activation from baseline, risk was associated with a decrease in TBET (milk) and increased IL4 (egg). Tolerance to egg was associated with current decreased CISH, and decreased TBET compared to baseline. However, the predictive capacity of the findingswasminimal, with only a few percentage points of risk being predicted by large changes in expression. CONCLUSIONS: Allergen-stimulated lymphocyte gene expression failed to significantly reflect allergy states over time.