Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens

Abstract

Background Peanut-allergic subjects have highly stable pathologic antibody repertoires to the immunodominant B cell epitopes of the major peanut allergens Ara h 1-3. Objective We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. Methods Measurements of total peanut-specific IgE (psIgE) and psIgG4 were made with CAP-FEIA. We analyzed sera from 22 OIT subjects and 6 controls and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1-3 using a high-throughput peptide microarray technique. Antibody affinity was measured using a competitive peptide microarray as previously described. Results At baseline, psIgE and psIgG4 diversity were similar between subjects and controls, and there was broad variation in epitope recognition. After a median 41 months of OIT, polyclonal psIgG4 increased from a median 0.3 mcg/mL (IQR 0.1-0.43) at baseline to 10.5 mcg/mL (3.95-45.48) (p<0.0001) and included de novo specificities. PsIgE was reduced from a median baseline of 85.45 kUA/L (23.05-101.0) to 7.75 kUA/L (2.58-30.55) (p<0.0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated subjects, several subjects generated new IgE specificities even as the total psIgE decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2. Conclusion OIT differentially alters Ara h 1-3 binding patterns. These changes are variable between subjects, not observed in controls, and include a progressive polyclonal increase in IgG4, with concurrent reduction in IgE amount and diversity.

Oral Immunotherapy for Food Allergy

“…Studies have consistently demonstrated specific immunologic changes, including increases in food-specific IgG4 and decreased basophil and mast cell responsiveness [13,14,18,56]. Some studies have shown alterations in the binding pattern of antigen to antigen-specific IgE, either by reduction in the diversity of epitope recognition or altered IgE affinity [57]. After 6-12 months of OIT, there appears to be a shift away from T H 2 cytokine production towards a proinflammatory profile characterized by increased production of IL-1β and TNF-α [18].…”

IgG4 and IgE Transcripts in Childhood Allergic Asthma Reflect Divergent Antigen-Driven Selection

“…The role of IgG4 in physiologic immune responses and in allergic diseases is under investigation. Some studies have found a negative correlation between IgG4 titers and symptom score (8)(9)(10)(11)(12)(13) and a positive correlation between IgG4 titers and IL-10-secreting APCs (14) following specific immunotherapy. Nouri-Aria et al (15) found that during specific immunotherapy, allergen-specific IgG4 serum levels increase 10-to 100-fold, and they conclude that grass pollen immunotherapy may induce allergen-specific, IL-10-dependent "protective" IgG4 responses.…”

Current opinion and review on peanut oral immunotherapy

“…34 There is promise for sustained unresponsiveness after discontinuation of OIT as published by Vickery et al 38 Twelve (50%) of 24 patients who completed the protocol were able to pass an OFC 1 month after discontinuation of OIT. 43 These patients were found to have lower specific IgE for peanut, lower ratios of peanut-specific IgE/total IgE, and smaller skin prick tests at baseline and at the end of the study. 43 In patients who failed the OFC after 1 month off OIT, the threshold of peanut protein required to elicit a response was above their initial baseline reacting dose.…”

“…43 These patients were found to have lower specific IgE for peanut, lower ratios of peanut-specific IgE/total IgE, and smaller skin prick tests at baseline and at the end of the study. 43 In patients who failed the OFC after 1 month off OIT, the threshold of peanut protein required to elicit a response was above their initial baseline reacting dose.…”