Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells.

Food allergy affects an estimated 8% of children in the United States. Oral immunotherapy (OIT) is a recently approved treatment, with outcomes ranging from sustained tolerance to food allergens to no apparent benefit. The immunological underpinnings that influence clinical outcomes of OIT remain largely unresolved. Using single-cell RNA-Seq and paired T cell receptor α/ß (TCRα/ß) sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper (Th) cells from 12 patients with peanut allergy longitudinally throughout OIT. We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into 6 clonally distinct subsets. Four of these subsets demonstrated a convergence of TCR sequences, suggesting antigen-driven T cell fates. Over the course of OIT, we observed suppression of Th2 and Th1 gene signatures in effector clonotypes but not T follicular helper-like (Tfh-like) clonotypes. Positive outcomes were associated with stronger suppression of Th2 signatures in Th2A-like cells, while treatment failure was associated with the expression of baseline inflammatory gene signatures that were present in Th1 and Th17 cell populations and unmodulated by OIT. These results demonstrate that differential clinical responses to OIT are associated with both preexisting characteristics of peanut-reactive CD4+ T cells and suppression of a subset of Th2 cells.

Frequent Versus Infrequent Bathing in Pediatric Atopic Dermatitis: A Randomized Clinical Trial.

BACKGROUND: Studies evaluating bathing frequency in pediatric atopic dermatitis (AD) are limited. Parents of children with AD often receive conflicting information, leading to frustration and confusion. OBJECTIVE: To evaluate efficacy of twice-daily soaking baths, followed by immediate application of an occlusive moisturizer (ie, soak-and-seal [SS]), versus twice-weekly SS baths, in the acute management of pediatric AD. METHODS: We conducted a randomized, single-blind, crossover-controlled trial comparing frequent versus infrequent SS baths, in children 6 months to 11 years of age with moderate-to-severe AD. Children were randomized 1:1 into 2 groups: group 1 underwent twice-weekly SS baths, for 10 minutes or less, over 2 weeks ("dry method" [DM]) followed by twice-daily SS baths, for 15 to 20 minutes, over 2 weeks ("wet method" [WM]). Group 2 did the inverse. Patients received the same moisturizer, cleanser, and low-potency topical corticosteroid (TCS). Primary outcome was AD severity evaluated using the SCORing Atopic Dermatitis (SCORAD) index. Caregiver assessment of AD severity (Atopic Dermatitis Quickscore [ADQ]), quality of life, Staphylococcal aureus colonization, skin hydration, moisturizer, and TCS usage were assessed. RESULTS: Of the 63 children screened, 42 fulfilled inclusion criteria and were randomized. Forty (95%) completed the study. WM decreased SCORAD by 21.2 compared with DM (95% confidence interval [CI], 14.9-27.6; P < .0001). Secondary analysis showed a greater than 30% SCORAD improvement for WM versus DM (McNemar's χ2 = 8.83, df = 1, P = .0030). SCORAD correlated with ADQ (r = 0.66), and ADQ also showed significant improvement with WM decreasing ADQ by 5.8 (95% CI, 1.8-9.7). No other secondary endpoints showed significance. CONCLUSIONS: As an acute treatment intervention, WM is superior to DM at improving disease severity in moderate-to-severe pediatric AD.