Elevated Levels Of NLRP3 In Cerebrospinal Fluid Of Patients With Autoimmune GFAP Astrocytopathy

BackgroundAutoimmune glial fibrillary acidic protein(GFAP)astrocytopathy is a common autoimmune disease of the central nervous system.The onset age is usually over 40 years old,with slightly more women than men.Similar to other autoimmune encephalitis,the main clinical signs and symptoms of this disease include fever,headache,involuntary movement,myelitis,visual abnormalities,ataxia,and other symptoms.This disease is diagnosed by detecting anti-GFAP immunoglobulin G(IgG)in cerebrospinal fluid(CSF).The specificity of antibodies against GFAP in serum remains to be studied.Magnetic resonance imaging(MRI)usually shows the characteristic linear perivascular radially enhanced foci in the brain,but they can still involve the optic nerve and spinal cord.At present,the pathogenesis of autoimmune GFAP astrocytic disease is not clear.Studies have shown that perivascular inflammatory cell infiltration is the most important feature in the anti-GFAP antibody associated idiopathic inflammatory lesions of the central nervous system(CNS),necrotizing meningoencephalitis and granulomatous meingoencephalitis.Therefore,we believe that neuroinflammation caused by the interaction of antibodies secreted by lymphocytes,microglias,macrophages,and plasma cells is the most likely pathogenesis of autoimmune GFAP astrocytosis.In the occurrence and development of diseases,cytokines are almost involved in the whole process of humoral immunity and cellular immunity.As objective and quantitative indicators,cytokines provide new ideas for the pathogenesis of diseases and become new biomarkers for anti-GFAP astrocytic diseases.ObjectiveExplore anti-GFAP astrocytes in cerebrospinal fluid in the patients with new biomarkers,analyse its relation with other existing clinical indexes,and compared with other category analysis,clear whether they can be used as the characteristic indexes,and analyze them in evaluating the severity of disease,treatment effect and prognosis.MethodsOur team formulate detailed plans:colltected clinical data,blood serum and cerebrospinal fluid samples from positive anti-GFAP patients,antibodies in serum and/or cerebrospinal fluid,from patients with viral encephalitis and other unrelated diseases.The anti-GFAP antibody titer and the concentrations of NLRP3 inflammasome,IL-1β,IL-6,IL-17 in CSF were determined by enzym-linked immunosorbency assay(ELISA).The severity of the disease was evaluated by extended disability scale(EDSS)score,and statistical analysis was performed by SPSS software.ResultsCompared with the control group,the levels of NLRP3 inflammasome,IL-1β,IL6,IL-17 and other substances in the cerebrospinal fluid of GFAP astrocytic patients were significantly increased(P<0.05).Compared with viral encephalitis group,the concentration of NLRP3 inflammasome in cerebrospinal fluid of GFAP astrocytic disease group was significantly increased(P<0.05).In the CSF and/or GFAP+groups,the concentrations of NLRP3 inflammasome in CSF were positively correlated with the concentrations of IL-1β,IL-6,and IL-17,and the concentrations of NLRP3 inflammasome,IL-1β,IL-6,and IL-17 were also positively correlated with EDSS scores.Compared with the CSF GFAP-group,the levels of NLRp3 inflammasome,IL1β,IL-17 and EDSS score were significantly increased in the CSF GFAP+group.Meanwhile,the anti-GFAP antibody titer in CSF was positively correlated with the concentrations of NLRp3 inflammasome,IL-1β,IL-17 and EDSS score,while there was no such difference in IL-6.Conclusion:Neuroinflammatory reaction and immune response play an important role in the pathogenesis of anti-GFAP astrocytosis.NLRP3 inflammasome in the cerebrospinal fluid of patients with GFAP astrocytic disease can be used as a biomarker to evaluate the severity of the disease and even to judge the prognosis of patients,which can provide a new idea for the future understanding and treatment of the disease.