The Expression And Clinical Significance Of SPD-1 And SPD-L1 In The Plasma And Cerebrospinal Fluid Of MS And NMOSD Patients

Objective:This study was to test the expression level of soluble programmed cell death protein 1(sPD-1)and soluble programmed cell death-ligand 1(sPD-L1)in plasma and cerebrospinal fluid(CSF)of multiple sclerosis(MS)、 neuromyelitis optica spectrum disorder(NMOSD)patients and compared with patients with noninflammatory neurological disorder(NND),and explore its clinical significance in MS、 NMOSD diseases,in order to provide new ideas for revealing the pathogenesis of MS and NMOSD and searching biomarkers and therapeutic targets.Methods:1、Patients: MS and NMOSD patients admitted to the outpatient and inpatient department of the Department of Neurology of the First Hospital of Jilin University between October 2021 and January 2023 were selected.There were 20 patients in acute stage and 11 patients in remission stage.All the enrolled patients met the newly published diagnostic criteria of MS and NMOSD,and the degree of neurological impairment was judged by extended disability status scale(EDSS)score.Meanwhile,16 patients in NND group matched with sex and age were selected.All patients did not use glucocorticoids,disease-modifying drugs(DMDs)drugs or immunosuppressants within 3 months before sample collection.All patients agreed and signed the informed consent form with the consent of themselves and their families.2 、 The expression of sPD-1 and sPD-L1 in plasma and CSF samples of patients was tested by double antibody sandwich enzyme-linked immunosorbent assay(ELISA).3、To analyze the correlation between the expression of sPD-1 and sPD-L1 in plasma and CSF and EDSS score and annual recurrence rate(ARR).Results:(1)The expression of sPD-1 in plasma of patients with MS in acute stage was significantly higher than that in patients with MS in remission stage(P<0.001)and in patients with NND(P<0.001).There was no obvious difference in the expression of sPD-1 in plasma between patients with remission stage of MS and NND;The expression of sPD-1 in plasma of patients with acute NMOSD was significantly higher than that in patients with NND(P=0.013).The expression of sPD-1 in plasma of patients with NMOSD in remission stage was not significantly different from that of patients with acute NMOSD and NND;There was no obvious difference in the expression of sPD-1 and sPD-1 in CSF among patients with MS and NMOSD in acute stage and NND group.(2)The expression of sPD-1 in plasma of MS patients was positively correlated with EDSS score(r=0.450,P=0.03)and ARR(r=0.519,P=0.011).However,the levels of sPD-1 in CSF of NMOSD patients,serum and CSF of NMOSD patients were not correlated with EDSS scores or ARR.(3)The expression of sPD-L1 in plasma of patients with MS and NMOSD in acute stage was significantly higher than that in remission phase patients(P=0.024;P=0.0022)and NND group(P=0.004;P=0.002).There was no obvious difference in the expression of sPD-L1 in plasma of the remission phase patients with MS,NMOSD and NND;While the expression of sPD-L1 in CSF of patients with MS and NMOSD in acute stage was significantly higher than that in NND group(P=0.0017;P=0.002).(4)The expression of sPD-L1 in plasma of MS patients was positively correlated with EDSS score(r=0.416,P<0.027),but there was no obvious correlation between the expression of sPD-L1 in plasma of MS patients,CSF and plasma of NMOSD patients and EDSS scores;The expression of sPD-L1 in plasma of NMOSD patients was positively related to ARR(r=0.531,P<0.011);There was no obvious relation between sPD-L1 level and ARR in CSF of NMOSD patients,plasma and CSF of MS patients.(5)The expression of sPD-1 in plasma of acute NMOSD patients was obviously lower than that in acute MS patients(P=0.0026),but the expression of sPD-1 in plasma was not different notably between the two groups in the remission phase;The expression of sPD-L1 in plasma was not different obviously between MS patients and NMOSD patients in acute and remission phase,and there was no obvious difference in the expression of sPD-1 and sPD-L1 in CSF between MS and NMOSD patients.(6)The sPD-L1 and sPD-1 levels in plasma was not different notably between OB positive and OB negative MS patients;sPD-L1 and sPD-1 levels in plasma was not different notably between AQP4-Ig G positive and AQP4-Ig G negative NMOSD patients.Conclusion:(1)The expression of sPD-1 in plasma of patients with acute MS was obviously higher than that of patients in remission stage and NND group;The expression of sPD-1 in plasma of NND group was obviously lower than that in acute NMOSD patients.(2)The expression of sPD-L1 in plasma of patients with MS and NMOSD in acute stage was obviously higher than that in remission stage and NND group;The expression of sPD-L1 in CSF of NND group was significantly lower than that in patients with MS and NMOSD in acute stage.(3)The expression of sPD-L1 and sPD-1 in plasma of MS patients was positively correlated with EDSS score,and the expression of sPD-1 was positively related to ARR;The expression of sPD-L1 in plasma of NMOSD patients was positively related to ARR.