Peanut Component‐Specific IgE and IgG4 Are Modulated by Sublingual Immunotherapy and Are Associated With Remission in 1–4‐Year‐Old Children

Background The safety and efficacy of 36‐month peanut sublingual immunotherapy (SLIT) was recently demonstrated in peanut‐allergic children (1–4 years old), with high remission rates three months post‐treatment. Methods We performed a post hoc analysis of longitudinal changes in peanut component‐specific IgE (PnC‐sIgE) and IgG4 (PnC‐sIgG4) levels in 1–4 year olds who underwent peanut SLIT to uncover immune mechanisms and potential biomarkers of remission. Plasma from 30 participants was analyzed at 0, 12, 24, 36, and 39 months using ImmunoCAP250 for PnC‐sIgE and PnC‐sIgG4 to Ara h 1, Ara h 2, Ara h 3, and Ara h 6 (Ah1‐6). Mixed‐effects models assessed longitudinal antibody changes, Wilcoxon tests compared antibody levels by remission status, and correlations evaluated age and baseline antibody levels. Results Peanut SLIT reduced IgE levels while increasing IgG4 levels specific to Pn and Ah1‐6 over 36 months. No changes in sIgE were observed in the placebo group, whereas increases in Pn‐, Ah1‐, and Ah3‐sIgG4 were noted. Participants achieving remission had lower IgE and IgG4 to Pn and Ah1‐6 at baseline and throughout 36 months of SLIT. Ah2‐sIgG4 showed no overlap between outcome groups at baseline, suggesting potential as a biomarker. Children under 3 had lower baseline Ah6‐sIgE and Ah1‐, Ah2‐, and Ah6‐sIgG4 levels and higher remission rates than those 3 and older, linking age, remission, and antibody profiles. Conclusion Component‐resolved analysis offers key insights into the immunological mechanisms in young children undergoing peanut SLIT, revealing lower baseline levels of Ah2‐sIgG4 as a potential biomarker of remission.