Longitudinal Antibody Responses to Peanut Following Probiotic and Peanut Oral Immunotherapy in Children With Peanut Allergy

To evaluate how a combined probiotic and peanut oral immunotherapy (PPOIT) alters peanut-specific IgE and IgG4 levels during treatment and their association to subjects’ ability to tolerate peanut after stopping PPOIT treatment, termed persistent sustained unresponsiveness (SU).

The study included longitudinal follow up of 48 children who participated in a double-blinded placebo-controlled (DBPC) trial that randomized 62 children ages 1 to 10 years with peanut allergy to receive PPOIT or placebo for 18 months.

In this trial, a DBPC food challenge (DBPCFC) with peanut was administered to all participants after the final day of treatment (T1). Any participant that passed this challenge was given a second DBPCFC 2 to 6 weeks after treatment to assess for SU (T2). Those who attained SU were instructed to ingest peanut ad libitum (as part of their normal diet) and were eligible for a long-term follow-up study and DBPCFC at 4 years posttreatment (T5). Serum levels of peanut and peanut component (Ara-h1, -h2, - h3, -h8 and -h9) IgE and IgG4 and salivary peanut IgA were measured.

At T2, SU was achieved in 82.1% and 3.6% for PPOIT and placebo respectively. At T5, 58% (7 of 12) in the PPOIT group and 7% (1 of 12) in the placebo group had achieved long term SU. PPOIT treatment was associated with significant decreases of peanut component IgE at T5 compared with placebo. PPOIT treatment was also associated with significantly higher levels of peanut component IgG4 and salivary peanut IgA at the end of treatment (T1) versus placebo but was not sustained long term, with no difference at T5. Subjects with persistent SU at T5 were found to have significantly lower 4-year post-treatment levels of peanut component IgE and IgG4 compared with participants who did not maintain SU.

PPOIT resulted in significant peanut-specific humoral changes compared with placebo. The acquisition and persistence of SU with PPOIT were significantly associated with decreases of peanut-specific IgE and IgG4.

Achieving long term SU after discontinuing peanut immunotherapy is an important outcome that has remained elusive. This small PPOIT trial had significantly higher rates of long-term SU and found that this outcome was associated with decreases in both peanut-specific IgE and IgG4, suggesting an overall downregulation of peanut-specific B cells in response to PPOIT.