Antigen-Specific IL-13 Secretion in Children with Eosinophilic Esophagitis

S U N D A Y 471 Development of Tolerance Following Peanut Immunotherapy Is Associated with Basophil Hyporesponsiveness and Low Peanut-IgE:IgG4 Ratio Michael D. Kulis, Jr, , PhD, Rishu Guo, PhD, Edwin Kim, MD, MS, Brian P. Vickery, MD, A. Wesley Burks, MD FAAAAI; University of North Carolina at Chapel Hill, Chapel Hill, NC. RATIONALE: Peanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant. We examined basophil responses and peanut-specific immunoglobulins to determine if these parameters were indicative of tolerance development. METHODS: Subjects enrolled in peanut OIT or SLIT protocols underwent double-blind placebo-controlled food challenges (DBPCFCs) with peanut to assess desensitization while continuing daily therapy. Subjects passing the DBPCFC were instructed to cease daily therapy and avoid all peanut products for 4 weeks, at which time a second DBPCFC was administered to assess tolerance. Basophil activation to peanut antigens, as well as serum peanut-specific IgE and IgG4 were measured at the time of desensitization DBPCFC. RESULTS: Tolerance was achieved in 5 of 12 (41.7%) subjects receiving SLIT, whereas 18 of 27 (66.7%) subjects were tolerant after receiving OIT. Basophil responses were significantly lower in the SLIT group that developed tolerance than in the non-tolerant SLIT group for each of 4 log-fold dilutions of peanut antigen used in the assay (p<0.05). Cumulatively 21 of 23 (91.3%) tolerant subjects had a peanut-IgE:IgG4 ratio below 0.92, while only 3 of 15 non-tolerant subjects had a ratio below 0.92; yielding an ROC curve with 91.3% specificity and 81.3% sensitivity. CONCLUSIONS: Development of tolerance following abstinence from peanut immunotherapy is possible and is associated with low basophil activation profiles and peanut-specific IgE:IgG4 ratio. Mechanistically, basophil suppression and the balance of antigen-specific IgE and IgG4may be important in the development of tolerance following peanut immunotherapy.