Kinetics of peanut-specific sIgE and sigg4 during oral immunotherapy (OIT) and remission of allergy.

Abstract

Background: Oral immunotherapy (OIT) is effective at inducing desensitisation and leads to remission in a subset of patients. Remission is a preferred outcome as it allows treatment cessation, free allergen intake, and substantial improvement in quality-of-life. The key immune changes during OIT that support remission remain poorly characterised. Advances have been hampered by restricted access to effective remission treatments, longitudinal biosamples, and long-term challenge-confirmed outcomes. Method(s): We examined longitudinal changes in peanut sIgE and sIgG4 in n = 283 children aged 1-10 years enrolled in three peanut OIT trials (PPOIT001, PPOIT002 and PPOIT003). Children received 18-months of peanut OIT (or placebo), and were followed for up to 66 months (4-years post-treatment). Plasma samples were obtained at pre-treatment (n = 278), end-of-treatment (n = 241), 1-year post treatment (n = 160) and 3-4 years post-treatment (n = 47). Remission was defined as passing a double-blind placebo-controlled food challenge (DBPCFC) at 4-8 weeks post-treatment. Children who received placebo provided a reference group. Linear models were used to compare log transformed immunoglobulin levels between groups at each time point. Mixed linear models were used to assess within group changes over time. Result(s): High dose peanut OIT with or without probiotic resulted in significant reductions in peanut sIgE, with no differences between these groups, indicating modulation of the underlying peanut-specific allergic response with both approaches. Baseline sIgE and sIgG4 levels were significantly lower in children who achieved remission compared to those who did not; however the sIgG4:sIgE ratio at baseline was significant higher in children who achieved remission compared to those who did not, suggesting that the balance of Th2/blocking Igs is an important factor determining the likelihood of remission. Importantly, peanut-sIgE levels in children with remission continued to reduce post-treatment, whereas levels in children who failed to achieve remission regressed towards baseline after treatment cessation Conclusion(s): Remission following high dose OIT is associated with lasting and continued reductions in allergen-sIgE. Lower baseline sIgE and sIgG4, and higher baseline sIgG4/sIgE ratio, may increase the likelihood of achieving remission. Lasting reductions in peanut-sIgE amongst children with remission supports the validity of a 4-8 week elimination period prior to DBPCFC for assessing remission of allergy.