Decrease in early basophil sensitivity to Ara h 2 correlates with sustained unresponsiveness in peanut oral immunotherapy

RATIONALE: Only some peanut-allergic subjects undergoing oral immunotherapy (OIT) achieve a sustained clinical benefit. We hypothesize basophil sensitivity early in OIT may be a useful biomarker in identifying those at risk for regaining allergic reactivity and be used for personalization of OIT.

METHODS: Peanut-allergic children, aged 7-13, enrolled in a single-center, open-label peanut OIT trial. After 1 year of OIT, 23 subjects with challenge-proven desensitization (post-OIT) underwent challenge after 1 month of avoidance (post-avoidance). Sustained unresponsiveness (SU) was confirmed in 9 patients. Peripheral blood from multiple time points was stimulated in vitro with Arah2, and the percent activated basophils by CD63 upregulation was assessed by flow cytometry. A data-driven analysis pipeline (R/Bioconductor) was used for derivation of ED50 and statistical analyses.

RESULTS: Post-OIT and post avoidance, ED50 is significantly more increased in SU than transient desensitization (TD), demonstrating decreased basophil sensitivity (p= 0.0041, p=0.0011). Basophil sensitivity decreases significantly from baseline after OIT and avoidance in SU (p= 0.0009, p= 0.0003). Post-avoidance, SU subjects have a 5-fold decrease in basophil sensitivity. At 3 months of OIT, basophil sensitivity in SU significantly decreases from baseline compared to TD (median 18-fold vs. 3-fold, p=0.01).

CONCLUSIONS: Basophil sensitivity significantly decreases in subjects with SU in OIT. We propose that the early decrease in basophil sensitivity during OIT, serving as a mechanistic biomarker of effective antibody responses, correlates with the chances of developing long-term clinical efficacy. We postulate that the use of this biomarker will help identify patients who require alternative forms of immunotherapy.