Elevated Cathepsin B enzyme levels: a potential risk indicator for rheumatoid arthritis: Insights from a Mendelian randomization study

Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly impacts the quality of life of affected individuals. Observational data have consistently pointed towards an associative relationship between cathepsins and the development of RA. Nonetheless, the establishment of a definitive causal nexus between members of the cathepsin family and the pathogenesis of RA remains elusive. In this study, we harnessed the principles of Mendelian randomization (MR) to interrogate the putative causal association between cathepsins and RA, and a series of sensitivity analyses were used to test the reliability of the MR results. Forward MR analyses substantiated a significant genetic correlation between the genetically predicted levels of Cathepsin B and the predisposition to RA, elevated levels of Cathepsin B exhibit a significant association with an increased risk of RA (OR = 1.0727, 95% CI: 1.0171-1.1314, P = .0098). In the reverse MR and multivariable MR analyses, no significant causal relationship was identified between cathepsins and RA. The findings suggest that Cathepsin B may serve as a biomarker for RA, thereby offering significant implications for the advancement of diagnostic and therapeutic strategies in the management of RA.