AUTHOR=Ma Xue , Wang Yao , Chen Xin , Guo Jun 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1418309

DOI=10.3389/fimmu.2024.1418309

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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, <italic>P</italic> = 0.037], IL-24 (OR: 161.37; 95% CI: 2.46–10569.21, <italic>P</italic> = 0.017), and C-C motif chemokine 19 (CCL19) (OR: 6.87, 95% CI: 1.78–26.93, <italic>P</italic> = 0.006).</p></sec><sec><title>Conclusion</title><p>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.</p></sec>