Development of Tolerance Following Peanut Immunotherapy Is Associated with Basophil Hyporesponsiveness and Low Peanut-IgE:IgG4 Ratio

Abstract

RationalePeanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant.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.MethodsSubjects 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.ResultsTolerance 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.ConclusionsDevelopment 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 IgG4 may be important in the development of tolerance following peanut immunotherapy. RationalePeanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant.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. 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allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant.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. MethodsSubjects 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. 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. ResultsTolerance 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. 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. ConclusionsDevelopment 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 IgG4 may be important in the development of tolerance following peanut immunotherapy. 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 IgG4 may be important in the development of tolerance following peanut immunotherapy.