Role of double-negative autoreactive cells (CD4^-CD8^-) in phosphatidylcholine-mediated rheumatoid arthritis: A Mendelian randomization study

Objective: Mendelian randomization (MR) was employed to explore the potential causal relationship between liposomes (LP) and rheumatoid arthritis (RA), with a focus on the mediating roles of immune cells (IC).

Methods: By screening public GWAS data, LP were used as exposure data, RA as outcome data, and IC as mediating factors. The Inverse Variance Weighted (IVW) method was the main analytical technique used in this paper to evaluate causal effects. Additional techniques included the MR-Egger, weighted median, weighted mode, and simple mode methods. Cochran's Q and MR-Egger were utilized for heterogeneity and multi-effect analysis.

Results: Phosphatidylcholine was revealed to enhance the risk of RA by MR analysis (P = 0.013, OR = 1.073, 95%CI = 1.015-1.136). There was no strong evidence that RA could affect liposome changes (IVW: P = 0.705, OR = 0.992, 95%CI = 0.952-1.034). The IVW method showed that increased levels of phosphatidylcholine were notably linked to higher levels of Double-Negative Autoreactive Cells (CD4^-CD8^-, DNAC) (P = 0.006, OR = 1.152, 95%CI = 1.041-1.276). The IVW approach showed that increased levels of DNAC were substantially linked to a higher risk of RA (P = 0.001, OR = 1.105, 95%CI = 1.041-1.173). Of the genetically predicted liposomes mediated by DNAC, 19.2 % were found.

Conclusion: The present work established a causal association between LP and RA, and identified a potential mediating influence of IC. However, the specific mechanism of LP triacyl-glycerol and IC on RA is still unclear, and further research is needed.