012 Transcriptomic profiling reveals a pronounced TH22 signature in dupilumab-associated face and neck dermatitis

Dupilumab, a therapeutic antibody that blocks the eczematous type 2 immune response in atopic dermatitis (AD), has shown efficacy many clinical trials and real-life observational studies. Besides blepharitis conjunctivitis, de novo appearance of head-neck is recognized as distinct side effect, occurring up to 10% patients at any time after dupilumab initiation. Histopathological features from conventional AD such psoriasiform hyperplasia or increased numbers ectatic capillaries suggest drug but exact underlying mechanisms remain largely unknown. We have thus profiled punch biopsies dupilumab-associated face neck (DAFND) by using single-cell RNA sequencing, compared data with untreated same region trunk, well healthy control individuals. found treatment was accompanied normalization IL-4/IL-13 activity markers CCL17, CCL18 CCL26 antigen-presenting cells myofibroblasts, confirming effective inhibition inflammation within DAFND lesions. Nevertheless, IL13 itself still considerably all groups, including skin. In addition, IL22, type17/type22-associated cytokine, significantly helper T trunk. By contrast, other 17-associated mediators IL17A IL26 were neither elevated nor dermatitis, while lesional skin trunk showed upregulation IL26. Our effectively dampens downstream IL4 receptor broad range leukocytes stromal lesions, concomitant 22-associated T-cell derived inflammation, which might be key drivers this effect.