NLRP3 level in cerebrospinal fluid of patients with neuromyelitis optica spectrum disorders: Increased levels and association with disease severity

Background: Neuromyelitis optica spectrum disorder (NMOSD) and MS are the most common autoimmune inflammatory demyelinating diseases of the CNS. However, the mechanisms of pathogenesis are still unclear. nucleotide-binding leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3), an important protein of the innate immune system that is activated by mitochondrial DNA (mtDNA), has been reported to be associated with various autoimmune disorders. Objective: To assess the levels of cerebrospinal fluid (CSF) NLRP3, mtDNA and inflammation-associated cytokines (IL-1 beta, IL-6 and IL-17) in patients with NMOSD and MS, and to examine the correlations between these factors. Methods: 28 NMOSD patients, 15 MS patients, and 16 controls with non-inflammatory neurological diseases were recruited. NLRP3 inflammasome, IL-1 beta, IL-6 and IL-17 were measured by ELISA. CSF extracellular mtDNA was measured by qPCR. The severity of clinical presentation was evaluated by EDSS score. Results: CSF levels of NLRP3, mtDNA, IL-1 beta, IL-6 and IL-17 were higher in NMOSD patients than in controls. Elevated CSF NLRP3, mtDNA and IL-6 were found in MS patients compared with controls. CSF NLRP3 and IL-6 levels were significantly higher in NMOSD patients than in MS patients. The EDSS scores of NMOSD patients during relapse were positively correlated with CSF NLRP3 and mtDNA. Conclusion: Our findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.