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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1406041

Investigating potential novel therapeutic targets and biomarkers for ankylosing spondylitis using plasma protein screening

Provisionally accepted
Wenkang You Wenkang You 1Mingzhong Liu Mingzhong Liu 1Yanbin Lin Yanbin Lin 2Zhangdian Lin Zhangdian Lin 1Rongjie Ye Rongjie Ye 1Canhong Zhang Canhong Zhang 1Rongdong Zeng Rongdong Zeng 1*
  • 1 Quanzhou First Hospital, Fujian Medical University, Quanzhou, China
  • 2 School of Medicine, Xiamen University, Xiamen, Fujian, China

The final, formatted version of the article will be published soon.

    Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and sacroiliac joints. Recent genetic studies suggest certain plasma proteins may play a causal role in AS development. This study aims to identify and characterize these proteins using Mendelian randomization (MR) and colocalization analyses. Methods: Plasma protein data were obtained from recent publications in Nature Genetics, integrating data from five previous GWAS datasets, including 738 cis-pQTLs for 734 plasma proteins. GWAS summary data for AS were sourced from IGAS and other European cohorts. MR analyses were conducted using "TwoSampleMR" to assess causal links between plasma protein levels and AS. Colocalization analysis was performed with the coloc R package to identify shared genetic variants. Sensitivity analyses and protein-protein interaction (PPI) network analyses were conducted to validate findings and explore therapeutic targets.We performed Phenome-wide association study (PheWAS) to examine the potential side effects of drug protein on AS treatment. Results: After FDR correction, eight significant proteins were identified: IL7R, TYMP, IL12B, CCL8, TNFAIP6, IL18R1, IL23R, and ERAP1. Elevated levels of IL7R, IL12B, CCL8, IL18R1, IL23R, and ERAP1 increased AS risk, whereas elevated TYMP and TNFAIP6 levels decreased AS risk. Colocalization analysis indicated that IL23R, IL7R, and TYMP likely share causal variants with AS. PPI network analysis identified IL23R and IL7R as potential new therapeutic targets. Conclusions: This study identified eight plasma proteins with significant associations with AS risk, suggesting IL23R, IL7R, and TYMP as promising therapeutic targets.Further research is needed to explore underlying mechanisms and potential for drug repurposing.

    Keywords: ankylosing spondylitis, Mendelian randomization, Plasma protein, therapeutic targets, biomarkers

    Received: 24 Mar 2024; Accepted: 25 Jul 2024.

    Copyright: © 2024 You, Liu, Lin, Lin, Ye, Zhang and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rongdong Zeng, Quanzhou First Hospital, Fujian Medical University, Quanzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.