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Investigating the causal relationship between immune factors and ankylosing spondylitis: insights from a Mendelian Randomization study.

Abstract

BACKGROUND: Despite previous studies indicating a close relationship between immune system and ankylosing spondylitis (AS), the causal relationship between them remains unclear. METHODS: Genome-wide association data were utilized to explore the causal link between 731 immune cells and AS using a bidirectional two-sample MR approach. The data included immune cell data from Orru et al.'s study and AS data from the FinnGen consortium. Cochran's Q test and leave-one-out checked instrument variable (IV) heterogeneity. IVW was the primary method for causal analysis, with MR-Egger and MR-PRESSO addressing horizontal pleiotropy. FDR correction was applied to both analysis directions to rectify multiple testing errors. RESULTS: In our study, 22 immune phenotypes out of 731 were casually linked to AS. After excluding 5 less robust features, 17 immune factors remained, with 4 being protective and the rest posing risks. Through FDR correction, we found a significant causal relationship between HLA DR on CD14- CD16+ monocyte and AS (OR (95%CI) = 0.70(0.60 ~ 0.83), P = 2.06*10-5). In the reverse analysis with AS as exposure, potential effects on 34 immune features were discovered. After correction, we confirmed significant causal relationships between AS and two immune features, namely CD20- B cell %lymphocyte (OR (95%CI) = 1.16(1.08-1.25), P = 1.91*10-5) and CD20- B cell %B cell (OR (95%CI) = 1.17(1.09-1.26), P = 1.50*10-5). CONCLUSIONS: Our study identified various features associated with AS in different types of immune cells. These findings provide important clues and a theoretical basis for further understanding the pathogenesis of AS, guiding clinical treatment, and drug design.

Authors: Geng Z, Tong Y, Chen Y, Wang J, Liu Z, Miao J, Li R,
Journal: Adv Rheumatol;2024Dec18; 64 (1) 89. doi:10.1186/s42358-024-00428-1
Year: 2024
PubMed: PMID: 39696529 (Go to PubMed)