Longitudinal antibody responses to peanut following probiotic and peanut oral immunotherapy in children with peanut allergy

Introduction Probiotic and Peanut Oral Immunotherapy (PPOIT) is effective at inducing sustained unresponsiveness (SU) at end-of-treatment and this effect persists up to 4 years post-treatment, referred to as persistent SU. We sought to evaluate (i) how PPOIT altered peanut-specific humoral immune indices, and (ii) how such longitudinal indices relate to persistent SU. Methods Longitudinal serum/plasma levels of whole peanut- and peanut component- (Ara-h1, -h2, -h3, -h8, -h9) specific-IgE (sIgE) and specific-IgG4 (sIgG4) antibodies were measured by ImmunoCAP and salivary peanut-specific-IgA (sIgA) by ELISA in children (n = 62) enrolled in the PPOIT-001 randomized trial from baseline (T0) to 4 years post-treatment (T5). Multivariate regression analyses of log-transformed values were used for point-in-time between group comparisons. Generalized estimating equations (GEE) were used for longitudinal comparisons between groups. Results Probiotic and Peanut Oral Immunotherapy was associated with changes in sIgE and sIgG4 over time. sIgE levels were significantly reduced post-treatment [T5, PPOIT vs. Placebo ratio of geometric mean (GM): Ara-h1 0.07, p = .008; Ara-h2 0.08, p = .007; Ara-h3 0.15, p = .021]. sIgG4 levels were significantly increased by end-of-treatment (T1, PPOIT vs. Placebo ratio of GM: Ara-h1 3.77, p = .011; Ara-h2 17.97, p < .001; Ara-h3 10.42, p < .001) but levels in PPOIT group decreased once treatment was stopped and returned to levels comparable with Placebo group by T5. Similarly, salivary peanut sIgA increased during treatment, as early as 4 months of treatment (PPOIT vs. Placebo, ratio of GM: 2.04, p = .014), then reduced post-treatment. Conclusion Probiotic and Peanut Oral Immunotherapy was associated with broad reduction in peanut-specific humoral responses which may mediate the clinical effects of SU that persists to 4 years post-treatment.