The levels of circulating cytokines and risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study.

ABSTRACT

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease affecting the central nervous system (CNS). NMOSD pathogenesis involves systemic inflammation. However, a causal relationship between circulating cytokine levels and NMOSD remains unclear. Methods: Mendelian randomization (MR) approaches were used to investigate the potential association between genetically determined circulating 19 inflammatory cytokines and 12 chemokines levels and the risk of developing NMOSD. Results: After Bonferroni correction, the risk of aquaporin 4-antibody (AQP4-ab)-positive NMOSD was suggested to be causally associated with the circulating levels of three cytokines, including interleukin (IL)-4 [odds ratio (OR) 11.01, 95% confidence interval (CI) 1.16-104.56, P = 0.037], IL-24 (OR 161.37; 95% CI 2.46-10569.21, P = 0.017), and C-C motif chemokine 19 (CCL19) (OR 6.87, 95% CI 1.78-26.93, P = 0.006). Conclusion: These findings suggest that a genetic predisposition to higher levels of IL-4, IL-24, and CCL19 may exert a causal effect on the risk of AQP4-ab-positive NMOSD. Further studies are warranted to clarify how these cytokines affect the development of AQP4-ab-positive NMOSD.