Longitudinal basophil activation testing for assessing response to low-dose initiation, slow-escalation peanut oral immunotherapy in patients with high Ara h 2-sIgE

Background Peanut oral immunotherapy (pOIT) can achieve desensitization, yet patients with high peanut-sIgE may experience more adverse reactions and treatment failure. We evaluated a conservative pOIT protocol in children with high Ara h 2-sIgE (≥40 kU/L) and examined longitudinal basophil activation test (BAT) and sIgE/sIgG4 trajectories as candidate biomarkers. Methods Thirty-two peanut-allergic children underwent pOIT, including 16 with high and 16 with lower Ara h 2-sIgE. All received low-dose initiation and slow up-dosing. Clinical outcomes, safety, and immunologic markers were evaluated longitudinally for up to 36 months. Results Effective desensitization (≥300 mg peanut protein) was achieved in 68.8% of high-sIgE and 62.5% of lower-sIgE participants. One severe adverse event occurred in each subgroup, with no treatment-related discontinuations. Peanut and Ara h 2/6-sIgE levels rose transiently before gradually declining, whereas sIgG4 increased early, leading to a reduced sIgE/sIgG4 ratio. A ratio <50 was associated with effective desensitization. BAT responses initially increased and subsequently declined, with progressive increase in the activation threshold. Baseline BAT and sIgE were not associated with desensitization. However, BAT area under the curve (AUC) <100 was significantly associated with effective desensitization with ROC AUC of 0.784 (bootstrap 95% CI 0.536–0.983). Exploratory time-lagged analyses did not establish prospective predictive utility. Conclusions Low-dose initiation, slow-escalation pOIT achieved effective desensitization in patients with high Ara h 2-sIgE, without treatment-related discontinuations. Longitudinal reductions in BAT and sIgE/sIgG4 ratio were associated with increased ingested dose. These exploratory biomarkers may provide adjunctive information during pOIT, but prospective validation is required.