The Study Of IL-35 Cell Subsets In Peripheral Blood Of Patients With Neuromyelitis Optica Spectrum Disorders

ObjectiveNeuromyelitis Optica spectrum disorders(NMOSD)is an autoimmune disease of the central nervous system,characterized by severe immune mediated demyelinating and axonal injury.The main target is the optic nerve and spinal cord.Interleukin-35(IL-35)is a negative immunoregulatory factor secreted by activated inflammatory cells,and plays an important role in maintaining immune homeostasis.The purpose of this study is to investigate the significance of IL-35 in the development of demyelinating disease in the central nervous system.Methods35 patients with NMOSD were recruited from the neurology department of Tianjin medical university general hospital from June 2016 to December 2017.At the same time,35 sex and age matched healthy subjects were selected as healthy controls(HCs).Samples were collected blood samples and record the basic situation of gender,age,height,weight,blood lipid,blood glucose and related immune indexes.Moreover,other basic information were recorded included spinal cord segments,disease onset age,course of disease,clinical symptoms and the Expanded Disability Status Scale(EDSS)of all patients with acute phase.Use cell-based immunofluorescence assay to detect Aquaporin-4 antibody(AQP4-Ab)in patients.The frequency of CD19~+CD138~+IL-35~+and CD4~+CD25~+IL-35~+in peripheral blood mononuclear cells was analyzed by flow cytometry.Mann-Whitney rank sum test was used to compare the difference between experimental group and HCs group.Spearman rank correlation analysis was used to analyze the correlation between IL-35~+cell frequency and clinical characteristics.P<0.05 thought the difference was statistically significant.Results1.Of the patients with NMOSD,there were 35 cases of serum AQP4-Ab examination,of which 11 cases were positive.2.The frequency of CD19~+CD138~+IL-35~+cells in PBMCs of NMOSD patients was 7.99±5.27,which was significantly lower than that of HCs,and the difference was statistically significant(P<0.05).3.The frequency of CD4~+CD25~+IL-35~+cells in PBMCs of NMOSD patients was 0.89±0.60,which was significantly lower than that of HCs,and the difference was statistically significant(P<0.05).4.The frequency of CD19~+CD138~+IL-35~+andCD4~+CD25~+IL-35~+cells in PBMCs of 35 NMOSD patients were negative correlated with the EDSS score,but there was no significant correlation with the recurrence rate,the annual recurrence rate,and the number of spinal cord segments.Conclusions1.NMOSD patients in acute phase of T,B cells secreted IL-35 significantly decreased,suggesting that IL-35 in the pathogenesis of NMOSD disease plays a role in inhibiting the inflammatory response,and is expected to become one of the inflammatory indicators of the acute phase of the disease.2.There was a significant negative correlation between the frequency of IL-35 cells and the EDSS score in the acute phase of NMOSD,suggesting that it might be a marker of the severity of NMOSD.