This Editors' Choice issue highlights six original studies covering: (1) ML-based prediction of the atopic march in >10,000 children with early-onset atopic dermatitis; (2) CD25 as a marker of activated MCTCs in chronic rhinosinusitis with nasal polyps; (3) long-term follow-up (~8–11 years) of the IMPACT peanut oral immunotherapy trial in children aged 1–3 years; (4) rates of new autoimmune diagnoses in children ages 6–17 with atopic disease on vs. off dupilumab (PEDSnet, 10 sites, 4-year follow-up); (5) dupilumab's effect on the EoE transcriptome across pediatric, adolescent, and adult patients; and (6) anti-α-Gal IgG antibodies as a mechanistic link between α-Gal sensitization and atherosclerosis.
Highlights across studies: - **Atopic march ML model:** Simplified models using routine early-life clinical features accurately predicted moderate-to-severe persistent asthma/allergic rhinitis by ages 5–11. - **Peanut OIT (IMPACT follow-up):** 80% of children who received pnOIT only (group A, n=40) were eating peanut at follow-up; 35% of group A reported peanut reactions since IMPACT; IgG4:IgE ratio remained higher in the pnOIT group vs. placebo years later. - **Dupilumab & autoimmunity in children:** Cutaneous autoimmune diagnoses (mainly psoriasis and alopecia areata) were ~2 per 1,000 children/year higher in the dupilumab group; no significant differences in endocrine, GI, or rheumatologic autoimmune diagnoses. - **EoE transcriptome:** Dupilumab normalized >1,300 dysregulated EoE genes (eosinophil and non-eosinophil pathways) across all age groups, sustained on treatment. - **α-Gal IgG & atherosclerosis:** Anti-α-Gal IgG formed immune complexes with α-Gal–bearing LDL, enhancing macrophage uptake and foam cell formation in vitro.
- The atopic march ML study and dupilumab/autoimmunity study are both EHR-based and observational, limiting causal inference and subject to coding/ascertainment bias. - The IMPACT long-term follow-up enrolled only 78 of 146 original participants (54%), introducing potential selection bias. - The α-Gal/atherosclerosis mechanism was demonstrated in vitro only; in vivo cardiovascular relevance remains unproven.
Early-life clinical features (respiratory symptoms, allergy meds, sensitization) can be used to flag young children with eczema for closer monitoring before asthma develops. Children on dupilumab should continue standard longitudinal monitoring for cutaneous autoimmune conditions such as psoriasis and alopecia areata, while being reassured that systemic autoimmune risks appear low.
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