Peanut oral immunotherapy modulates immunoglobulins in saliva
Published: August 5, 2022
Peanut oral immunotherapy (PnOIT) was recently approved by the FDA for peanut allergy, following a successful Phase 3 trial. Several immune markers have been quantified in the serum throughout therapy, including peanut-specific IgE, IgG4, and IgA. Typically, peanut-specific IgE increases initially and then decreases later in therapy, while peanut-specific IgG4 and IgA increase sharply and throughout therapy. While these changes are consistently observed with treatment, they are poor biomarkers to predict OIT outcomes. However, since OIT is administered at the oral and gastrointestinal mucosal surfaces, antigen-specific immunoglobulin responses at these sites may be more informative.
In a paper recently published in The Journal of Allergy and Clinical Immunology: In Practice, Smeekens et al quantified salivary peanut-specific and total IgG4 and IgA in participants from the Immune Tolerance Network’s IMPACT study, a phase 2 randomized, placebo-controlled trial of PnOIT. Briefly, children aged 12-48 months with double-blind, placebo-controlled food challenge (DBPCFC)-confirmed peanut allergy were assigned to either peanut oral immunotherapy or placebo for 134 weeks. Participants that completed the protocol were assessed for remission after 6 months of avoidance, at week 160. Participants that passed the DBPCFCs at weeks 134 and 160 were categorized as desensitized/remission, participants that passed the DBPCFC at week 134 but failed at week 160 were categorized as desensitized/no remission, and participants that did not pass the DBPCFC at week 134 were categorized as not desensitized/no remission. Saliva and serum were collected at baseline, 30, 82, 134 and 160 weeks, and salivary peanut-specific and total IgG4 and IgA were quantified by ELISA.
Participants who received PnOIT had increased peanut-specific IgG4 and IgA in saliva compared to participants who were on placebo. During PnOIT, desensitized participants had increased peanut-specific IgA that plateaued, whereas the not desensitized/no remission group did not change over time. Interestingly, when the PnOIT group was evaluated by clinical outcome, peanut-specific IgA was higher at baseline in the not desensitized/no remission group compared to the desensitized/remission group, suggesting that the increase in IgA production rather than the quantity is indicative of desensitization. Salivary peanut-specific IgG4 was compared to serum levels, and there was a high correlation between local and systemic peanut-specific IgG4 production. Here, although the sample size of groups stratified by clinical outcome was relatively small, the authors demonstrated that high levels of peanut-specific IgA in saliva at baseline may indicate decreased likelihood of desensitization, which would be an impactful predictor. Similarly, increases in peanut-specific IgA within 30 weeks of starting OIT may be utilized to monitor successful outcomes. These data provide insight into OIT-induced mucosal responses and suggest the utility of these easily obtained samples for biomarker development.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.