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Florian Anzengruber,1,2 Adhideb Ghosh,1–3 Julia-Tatjana Maul,1,2 Mathias Drach,1,2 Alexander A Navarini1–3 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; 2Faculty of Medicine, University of Zurich, Zurich, Switzerland; 3Competence Center Personalized Medicine University of Zurich/Swiss Federal Institute of Technology (ETH) Zurich, Switzerland Purpose: Several studies have suggested that an HLA-Cw6+ allele can predict an improved outcome of treatment in psoriasis patients. The aim of the study was to assess whether the published association between HLA-Cw6 allele carriers and response to ustekinumab has the potential to impact treatment decisions. Patients and methods: Differences in Psoriasis Activity and Severity Index 50, 75, and 90; Nail Psoriasis Severity Index; and Dermatology Life Quality Index at 16 weeks were evaluated between HLA-Cw6 allele carriers vs. non-carriers. Thirty patients with moderate-to-severe psoriasis under treatment with ustekinumab were included in our study. Results: There was no difference between the two groups with respect to Psoriasis Activity and Severity Index 50, 75, and 90 or in terms of change in Nail Psoriasis Severity Index or Dermatology Life Quality Index. Conclusion: In our retrospectively analyzed cohort, we could not detect the previously reported better response in HLA-Cw6+ vs. HLA-Cw6− patients. Keywords: human leukocyte antigen, Cw6, genetic variations, HLA-Cw6, ustekinumab

Psoriasis is a common, relapsing inflammatory skin disease characterized by erythematous scaly plaques. Histological manifestations of psoriasis include keratinocyte dysregulation and hyperproliferation, elongated rete ridges, and inflammatory infiltrates consisting of T cells, macrophages, dendritic cells, and neutrophils. Despite the availability of new effective drugs to treat psoriasis, the underlying mechanisms of pathogenesis are still poorly understood. Recent studies have shown that Aldara cream, used to treat benign skin abnormalities, triggers psoriasis-like disease in humans and mice and have implicated Th17 cells in disease initiation. Using this as a model, we found a predominant role for the Th17 signature cytokines IL-17A, IL-17F, and IL-22 in psoriasiform plaque formation in mice. Using gene-targeted mice, we observed that loss of Il17a, Il17f, or Il22 strongly reduced disease the severity of psoriasis. However, we found that Th17 cells were not the primary source of these pathogenic cytokines. Rather, IL-17A, IL-17F, and IL-22 were produced by a skin-invading population of γδ T cells and RORγt(+) innate lymphocytes. Furthermore, our findings establish that RORγt(+) innate lymphocytes and γδ T cells are necessary and sufficient for psoriatic plaque formation in an experimental disease model that closely resembles human psoriatic plaque formation. [ABSTRACT FROM AUTHOR]