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Abstract

Biological therapies are becoming increasingly important for the treatment of psoriasis. However, clinical outcomes remain variable, which may reflect the molecular heterogeneity of disease. Patient characteristics which might be predictive of response to specific treatments would be useful to guide selection of biological therapies. In this study, we assessed whether staining for inflammatory cytokines and nitric oxide synthase 2 correlate with clinical response. A retrospective chart and slide review was performed across two academic institutions (2014-2023). We analyzed pre-treatment biopsies from 17 patients with psoriasis treated antibodies targeting the IL17A cytokine or the IL17A receptor subunit. RNA in situ hybridization was used to measure markers of type 3 (IL17A, IL17F) and type 2 (IL13) inflammation, as well as nitric oxide synthase 2 (NOS2). Blinded quantification was performed by a board-certified dermatopathologist. Patterns were compared among responders (n=12) and non-responders (n=5) as determined by change in body surface area involvement following treatment. We found that increased NOS2 expression was significantly associated with treatment failure with anti-IL17 biological therapies, while IL17A expression was associated with optimal treatment response. In contrast, IL17F and IL13 expression were not significantly different between groups. Limitations include retrospective design, small sample size, and potential use of concomitant therapies. Overall, these data suggest that baseline IL17A and NOS2 levels as detected by RNA in situ hybridization may be useful for the selection of optimal biological therapies for the treatment of psoriasis. This study expands the potential for personalized medicine for inflammatory skin disorders.