The Proportion And Significance Of Myeloid-derived Suppressor Cells In Peripheral Blood Of Patients With Neuromyelitis Optica Spectrum Disorders

Background and Objective:This research detected the proportion of MDSCs and their subgroups of patients with neuromyelitis optica spectrum disorders（NMOSD）in the acute phase and after methylprednisolone sodium succinate therapy,then we analyzed the correlation of MDSCs with serum IL-6 level and clinical indicator of patients.This study aim to preliminarily discuss the role of MDSCs in the pathogenesis of NMOSD and expect to provide pathogenetic theory and immunological target therapy for NMOSD.Methods:The inclusion and exclusion criteria of NMOSD patients were designed,and the basic information,clinical indicators,laboratory and imaging information of the patients were statistically tracked.Flow cytometry was used to detect the percentages of MDSCs and their subsets of NMOSD patients at the acute phase and at the ninth day of methylprednisolone therapy,and then the percentages of MDSCs and their subsets were compared with HC.ELISA was used to detect the expression level of IL-6 in serum of NMOSD and HC group.Results:（1）Compared with HC,the percentage of MDSCs（HLA-DR^-CD11b⁺）in PBMC was significantly increased in patients with acute NMOSD and acute NMOSD treated with methylprednisolone on day 9.The percentage of MDSCs in PBMC was significantly increased on day 9 of methylprednisolone compared with before the treatment.Compared with HC,the percentage of G-MDSCs（HLA-DR^-CD11b⁺CD66b⁺CD14^-）in the total MDSCs of acute phase and methylprednisolone on day 9 were significantly increased.The percentage of G-MDSCs in total MDSCs was significantly increased on day 9 of methylprednisolone than before the treatment.There was no significant difference in the percentage of M-MDSCs（HLA-DR^-CD11b⁺CD14⁺CD66b^-）in total MDSCs among this three groups.（2）There was no significant correlation between the percentage of MDSCs in PBMC and the percentage of subtype（G-MDSCs and M-MDSCs）in MDSCs with EDSS score and ARR at the NMOSD acute phase.（3）Serum IL-6 of patients with acute NMOSD was significantly higher than HC;There was no significant correlation between serum IL-6 level and EDSS,ARR in NMOSD patients at acute phase.（4）The correlation analysis between serum IL-6 level and the percentage of MDSCs in PBMC showed that the serum IL-6 level in patients with acute NMOSD was positively correlated with the percentage of MDSCs in PBMC.Results showed that there was no significant correlation between serum IL-6 level and G-MDSCs and M-MDSCs in MDSCs of NMOSD patients at acute phase.（5）AQP4 titer of NMOSD patients was positively correlated with EDSS score,but had no significant correlation with ARR.（6）AQP4 titer was positively correlated with IL-6 in serum of NMOSD patients;There was a positive correlation between AQP4 titer and the percentage of MDSCs in PBMC,but no significant correlation between AQP4 titer and the percentage of G-MDSCs in MDSCs and the percentage of M-MDSCs in MDSCs.Conclusion:（1）MDSCs participate in the occurrence,development and outcome of NMOSD.（2）In NMOSD,G-MDSCs subsets are more susceptible to changes in the inflammatory microenvironment than M-MDSCs,and may play a more important immune regulation role in NMOSD.（3）IL-6 is an important pro-inflammatory factor involved in NMOSD,it can induce the production of AQP4 antibodies,aggravating the disease process.In NMOSD,IL-6 may be an important inflammatory factor that promotes the expansion of MDSCs.（4）As an immature and heterogeneous population,the function of MDSCs are susceptible to changes in different microenvironments.Therefore,in NMOSD,the specific role and mechanism of this cell in each phase need to be further explored.