Causal associations between circulating immune cells and osteoarthritis: A bidirectional mendelian randomization study

Purpose: Osteoarthritis (OA) is a common degenerative joint disease, with its etiology remaining poorly understood. Our study aims to explore the causal associations between immune cells and OA, with the goal of generating a new perspective for targeted intervention strategies. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was performed to estimate the causality between multiple circulating immune cells and different sites of OA. The immune cell traits analyzed included the counts of circulating white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils, and basophils, as well as certain subsets of T and B lymphocytes. The OA types included were OA at any site, knee OA, hip OA, spine OA, thumb OA, and hand OA. Inverse-variance weighted (IVW), MR-Egger, weight median and weight mode were used to evaluate causal effects, with IVW being the main analysis method. Sensitivity analyses were conducted to assess heterogeneity and pleiotropy. Results: Our findings indicated that resting regulatory T cell (Treg) absolute counts (AC) were causally associated with an increased risk for spine OA [odds ratio (OR), 1.051; 95 % confidence interval (CI), 1.018-1.086; P=0.0005, P-FDR=0.0350], and spine OA showed a positive causal relationship with the neutrophils count (OR, 1.104; 95 %CI, 1.032-1.181; P=0.0039, P-FDR=0.0233). Besides, OA at any site was correlated with a rise in circulating eosinophils count (OR, 1.05; 95 %CI, 1.021-1.079; P=0.0007, P-FDR=0.0041), while knee OA was associated with decreased total WBC (OR, 0.945; 95 %CI, 0.912-0.979; P=0.0016, P-FDR=0.0048) and monocytes counts (OR, 0.958; 95 %CI, 0.934-0.982; P=0.0007, P-FDR = 0.0041). No evidence of heterogeneity or horizontal pleiotropy was detected. Conclusions: Our study has demonstrated the causal associations between multiple immune cells and diverse joint OA. These results highlight the intricate interplay between immune cells and OA, suggesting potential targets for therapeutic interventions to manage disease progression and alleviate symptoms.