Unlocking the role of the B7‐H4 polymorphism in psoriasis: Insights into methotrexate treatment outcomes: A prospective cohort study

Abstract

AbstractB7‐H4 is a recently discovered member of B7 family that negatively regulates T‐cell immunity, specifically Th1 and Th17 cell responses. However, its role in the pathogenesis of psoriasis has yet to be determined. This study aims to investigate the effect of B7‐H4 polymorphism on the efficacy of methotrexate (MTX) and its mechanism in psoriasis. Four single nucleotide polymorphisms of B7‐H4 were genotyped in 310 psoriatic patients who received 12‐week MTX. The protein expression of B7‐H4 in platelets was characterized using immunofluorescence staining, confocal laser scanning microscopy, and flow cytometry techniques. We found that GG genotype carriers of B7‐H4 rs1935780 had a lower Psoriasis Area and Severity Index (PASI) 75 response rate and higher weight (p = 0.0245) and body mass index (p = 0.0185) than AA and AG genotype carriers. Multiple regression analysis showed that the PASI score at baseline (p = 0.01) and age at disease onset (p = 0.003) were positively correlated with PASI 75 response rate, while weight (p = 0.005) and the rs1935780 genotype (p = 0.003) were negatively associated with PASI 75 response rate. B7‐H4 was expressed in the platelet plasma membrane and cytoplasm. Furthermore, the expression of B7‐H4 protein in platelets was lower in good responders than in non‐responders and was upregulated considerably after 12‐week MTX or in vitro MTX stimulation in good responders. Collectively, these results demonstrate that psoriatic patients with GG genotype of B7‐H4 rs1935780 had a poorer response to MTX. Low expression of B7‐H4 protein in platelets correlated with better clinical outcomes of MTX in psoriasis.