Wang, Bing; Wang, Zhicheng; Yang, Wenjing; Han, Ling; Huang, Qiong; Yawalkar, Nikhil; Zhang, Zhenghua; Yao, Yu; Yan, Kexiang (2024). Unlocking the role of the B7-H4 polymorphism in psoriasis: Insights into methotrexate treatment outcomes: A prospective cohort study. Immunology, 171(1), pp. 104-116. Wiley-Blackwell 10.1111/imm.13704
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Immunology_-_2023_-_Wang_-_Unlocking_the_role_of_the_B7_H4_polymorphism_in_psoriasis_Insights_into_methotrexate_treatment.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (1MB) |
B7-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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology |
UniBE Contributor: |
Yawalkar, Nikhil |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0019-2805 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Oct 2023 11:33 |
Last Modified: |
06 Dec 2023 00:16 |
Publisher DOI: |
10.1111/imm.13704 |
PubMed ID: |
37814391 |
Uncontrolled Keywords: |
B7-H4 methotrexate platelets psoriasis rs1935780 |
BORIS DOI: |
10.48350/187077 |
URI: |
https://boris.unibe.ch/id/eprint/187077 |
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