The Serum Levels And Clinical Significance Of ET-1 In Patients With Neuromyelitis Optica Spectrum Disorders

Objective Neuromyelitis Optica Spectrum Disorders(NMOSD)are inflammatory demyelinating diseases of central nervous system(CNS)which mediated by autoantibodies and involved by various immune components.Endothelin-1(ET-1)is a potent vasoconstrictor and has been found to participate in inflammatory responses and play a pro-inflammatory role in a variety of autoimmune diseases.The purpose of this study was to measure serum levels of ET-1 and other immune-related cytokines/chemokines in patients with NMOSD,and to analyze the correlations between serum ET-1 levels and clinical parameters in patients with NMOSD.Methods Thirty-eight patients with NMOSD during acute phase and twenty-eight healthy controls(HCs)were recruited.Demographic information and clinical data of each subject were collected,including age,gender,anti-AQP4 antibodies,disease course,etc.Expanded Disability Status Scale(EDSS)score was used to evaluate the disability status of patients.The involved intracranial and spinal cord lesions were evaluated by nuclear magnetic resonance imaging(MRI).Serum levels of ET-1 in patients with NMOSD and healthy controls were measured by ELISA.The cytometric bead array was used to detect serum levels of immune-related cytokines/chemokines in patients with NMOSD.The correlations between serum ET-1 levels with clinical parameters and immune-related cytokines/chemokines were analyzed.Binary logistic regression analysis was used to evaluate the independence of different factors for predicting NMOSD.The receiver operating characteristic curve was used to evaluate the diagnostic value of ET-1 in NMOSD.Results 1.Serum ET-1 levels in patients with NMOSD were significantly higher than those in HCs(1.30 ± 0.07 pg/ml vs 0.93 ± 0.08 pg/ml),and the difference was statistically significant(P = 0.0001).2.Serum ET-1 levels in patients with NMOSD were positively correlated with the score of EDSS(r = 0.428,P = 0.0183).3.Serum levels of IL-4(P < 0.0001),IL-2(P < 0.0001),IL-1β(P = 0.0005),TNF-α(P = 0.0025),IL-6(P < 0.0001),IFN-γ(P = 0.0005),IL-10(P < 0.0001)in patients with NMOSD were significant increased compared to HCs.No significant differences were found in serum levels of IP-10、MCP-1、IL-17A、IL-12p70、IL-8 and TGF-β1 in patients with NMOSD compared to HCs.There were no significant correlations between serum ET-1 levels and the above seven upregulated cytokines.4.Serum levels of ET-1(P = 0.0335)and IL-6(P = 0.0214)were significantly downregulated after IVMP treatment,whereas serum levels of IL-10 were significantly elevated after IVMP treatment(P = 0.0131).5.In the logistic regression model,serum ET-1,IL-6,and IL-10 may be predictors of NMOSD diagnosis.Conclusions 1.ET-1 may play a pro-inflammatory role in pathological process of NMOSD.2.Serum ET-1 levels may be associated with the severity of NMOSD.3.There were no significant correlations between serum ET-1 levels and immune-related cytokines/chemokines,implying that it was not clear whether changes in ET-1 levels were primary or secondary in the pathological process of NMOSD.4.The inflammatory cytokine IL-6 may play a pro-inflammatory role while IL-10 may play an anti-inflammatory role in NMOSD.5.ET-1 may be a potential biomarker with diagnostic value for NMOSD.But its diagnostic accuracy was lower than IL-6.