Use of IgE and IgG4 epitope binding to predict the outcome of oral immunotherapy in cow's milk allergy

Abstract

Background Oral immunotherapy (OIT) with cow's milk (CM) has been reported to induce a number of specific antibody responses, but these remain to be fully characterized. Our objective was to explore whether IgE and IgG4 epitope binding profiles could predict the risk of side effects during cow's milk OIT. Methods The study population consisted of 32 children (6 – 17 years of age) with cow's milk allergy: 26 children who successfully completed OIT and 6 children who discontinued therapy due to adverse reactions. We investigated sera drawn before and after OIT. We analyzed specific IgE and IgG4 binding to CM protein derived peptides with a microarray based immunoassay. Antibody binding affinity was analyzed with a competition assay where CM proteins in solution competed with peptides printed on the microarray. Results IgE binding to CM peptides decreased and IgG4 binding increased following the OIT in children who attained desensitization. Compared with children who successfully completed OIT, those who discontinued OIT due to adverse reactions developed increased quantities and affinity of epitope-specific IgE antibodies and a broader diversity of IgE and IgG4 binding, but less overlap in IgE and IgG4 binding to CM peptides. Conclusions Detailed analysis of IgE and IgG4 binding to CM peptides may help in predicting whether CM OIT will be tolerated successfully. It may thus improve the safety of the therapy.

Common food allergens and their IgE-binding epitopes

“…34 AA16e35 and AA34e53 in k-casein were also Time-related differences in the binding of IgE and IgG4 to epitopes of b-lactoglobulin, a-lactalbumin, and caseins between patients with early recovery or persistent cow's milk allergy have been investigated. 101,102 Furthermore, IgE and IgG4 epitope binding was also analyzed to predict the outcome of oral immunotherapy in cow's milk allergy using peptide arrays. 103 The results of this study showed that monitoring the binding of IgE and IgG4 to epitope peptides of caseins has predictive value for the development of tolerance to cow's milk or the outcome of oral immunotherapy.…”

Molekular-allergologische Aspekte der allergenspezifischen Immuntherapie

“…Neuere Untersuchungen gibt es bereits auf Epitopebene aus derselben Arbeitsgruppe: Mithilfe eines Microarrays, basierend auf Peptiden der Kuhmilcheinzelallergene, konnten Savilahti et al [38] zeigen, dass ein breiteres Spektrum von IgE-Reaktivitäten und eine höhere Konzentration peptidspezifischer IgE vor SOTI mit Kuhmilch einen Prädiktor für Therapienebenwirkungen und das Ausbleiben des Therapieerfolgs darstellten [38].…”

Oral Immunotherapy for Food Allergies

“…In a trial of milk OIT, the investigators found decreased IgE binding and increased IgG 4 binding to cow milk epitopes among children who achieved desensitization. Those who discontinued OIT due to adverse effects had increased quantity and affinity of epitope-specific IgE antibodies and less overlap between IgE and IgG 4 binding to milk peptides [62] . These results suggest that analysis of IgE and IgG4 binding to allergens and their specific epitopes may assist in predicting outcomes and improving the safety of OIT.…”