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However, its role in the pathogenesis of psoriasis has yet to be determined. This study aims to investigate the effect of B7\u2010H4 polymorphism on the efficacy of methotrexate (MTX) and its mechanism in psoriasis. Four single nucleotide polymorphisms of B7\u2010H4 were genotyped in 310 psoriatic patients who received 12\u2010week MTX. The protein expression of B7\u2010H4 in platelets was characterized using immunofluorescence staining, confocal laser scanning microscopy, and flow cytometry techniques. We found that GG genotype carriers of B7\u2010H4 <jats:italic>rs1935780<\/jats:italic> had a lower Psoriasis Area and Severity Index (PASI) 75 response rate and higher weight (<jats:italic>p<\/jats:italic>\u2009=\u20090.0245) and body mass index (<jats:italic>p<\/jats:italic>\u2009=\u20090.0185) than AA and AG genotype carriers. Multiple regression analysis showed that the PASI score at baseline (<jats:italic>p<\/jats:italic>\u2009=\u20090.01) and age at disease onset (<jats:italic>p<\/jats:italic>\u2009=\u20090.003) were positively correlated with PASI 75 response rate, while weight (<jats:italic>p<\/jats:italic>\u2009=\u20090.005) and the <jats:italic>rs1935780<\/jats:italic> genotype (<jats:italic>p<\/jats:italic>\u2009=\u20090.003) were negatively associated with PASI 75 response rate. B7\u2010H4 was expressed in the platelet plasma membrane and cytoplasm. Furthermore, the expression of B7\u2010H4 protein in platelets was lower in good responders than in non\u2010responders and was upregulated considerably after 12\u2010week MTX or in vitro MTX stimulation in good responders. Collectively, these results demonstrate that psoriatic patients with GG genotype of B7\u2010H4 <jats:italic>rs1935780<\/jats:italic> had a poorer response to MTX. Low expression of B7\u2010H4 protein in platelets correlated with better clinical outcomes of MTX in psoriasis.<\/jats:p>","DOI":"10.1111\/imm.13704","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T02:32:12Z","timestamp":1697077932000},"page":"104-116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unlocking the role of the B7\u2010H4 polymorphism in psoriasis: Insights into methotrexate treatment outcomes: A prospective cohort study"],"prefix":"10.1111","volume":"171","author":[{"given":"Bing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University, Shanghai Institute of Dermatology  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Huashan Hospital Fudan University  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