Causal Relationship of Immune Cells and Metabolites in Ankylosing Spondylitis: A Mendelian Randomization Analysis

OBJECTIVE: This study aims to analyze the immune metabolism mechanism of Ankylosing Spondylitis (AS) and explain the causal relationship between immune cells and metabolites in the progression of AS disease through Mendelian randomization (MR) analysis, providing a theoretical basis for targeted therapy. METHODS: The causal relationship between 486 metabolites and 731 immunophenotypes and AS was evaluated by the two-step MR method, and key mediating variables were screened. RESULTS: Univariate MR identified 42 immunophenotypes and 8 metabolites that were significantly associated with the risk of AS. Two-step MR showed that the proportion of CD33dim HLA DR+ CD11b- %CD33dim HLA DR+ cells decreased, the secretion level of betaine increased, and the risk of AS increased significantly. CONCLUSION: It was found that immune cells CD33dim HLA DR+ CD11b- %CD33dim HLA DR+ and its metabolite betaine have a causal relationship with the occurrence and development of AS, which is worth verifying in the clinical diagnosis and treatment of AS.