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

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.To assess the levels of cerebrospinal fluid (CSF) NLRP3, mtDNA and inflammation-associated cytokines (IL-1β, IL-6 and IL-17) in patients with NMOSD and MS, and to examine the correlations between these factors.28 NMOSD patients, 15 MS patients, and 16 controls with non-inflammatory neurological diseases were recruited. NLRP3 inflammasome, IL-1β, 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.CSF levels of NLRP3, mtDNA, IL-1β, 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.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.