The Expression And Clinical Significance Of Fibroblast Growth Factor 2 And 21 In The Serum And Cerebrospinal Fluid Of MS And NMOSD Patients

Objective:This study aims to analyze and compare the expression and clinical significance of fibroblast growth factor(FGF)2 and FGF21 in serum and cerebrospinal fluid(CSF)of multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD)patients with serum and CSF of non-inflammatory neurological disorder(NND)patients.At the same time,we also explore their correlation with the severity of MS and NMOSD.Subjects and methods:We recruited a total of 31 MS and NMOSD patients respectively.Among them,20 patients were in acute relapse stage and 11 patients were in remission stage.Those patients were selected from both the outpatient department and inpatient department of the Department of Neurology of the First Hospital of Jilin University between October 2019 and May 2021.All the enrolled patients were diagnosed by two neuroimmunological physicians according to the latest MS and NMOSD diagnostic criteria,and all of them were clinically confirmed.Also,we assessed the severity of every enrolled patients by using the Expanded Disability Status Scale(EDSS).At the same time,16 gender and age matched NND patients were recruited.All enrolled patients were not treated with glucocorticoid,disease modifying therapy(DMT)drugs or immunosuppressive agents within 3 months prior to sample collection.All the subjects provided written informed consent.(1)The expression levels of serum and CSF FGF2 and FGF21 in enrolled patients were detected by commercial enzyme linked immunosorbent assay(ELISA)kits according to the manufacturer’s instruction.(2)To analyze the correlation between serum and CSF FGF2 and FGF21 levels andVannualized relapse rate(ARR)as well as EDSS score.Result:(1)The level of FGF2 in serum was significantly higher in both relapse and remission phase patients with MS and NMOSD compared to the NND group,and there was no statistically significant difference in serum FGF2 levels between the relapse and remission phase patients with MS and NMOSD;the level of FGF2 in CSF of patients in the relapse stage of MS was significantly higher than that of the NND group,and there was no statistically significant difference in the level of FGF2 in CSF between patients in the relapse stage of NMOSD and NND group.(2)There was no significant correlation between the levels of serum and CSF FGF2 levels and ARR in MS patients;the level of FGF2 in CSF was negatively correlated with ARR in patients with NMOSD,but there was no significant correlation between the level of serum FGF2 and ARR;the levels of FGF2 in serum and CSF both of MS and NMOSD patients were not significantly correlated with EDSS scores.(3)The serum FGF21 level in patients with remission stage of MS was significantly lower than those in the NND group,but there was no significant difference in serum FGF2 level between patients in relapse stage of MS,patients in remission stage of MS and patients with NND;there was no significant difference in serum FGF21 level between relapse stage of NMOSD patients,remission patients and NND patients;there was no significant difference in the level of FGF21 in CSF between both in relapse stage of MS and NMOSD patients and NND group.(4)The level of FGF21 in CSF of MS patients was positively correlated with ARR,but there was no significant correlation between the level of FGF21 in serum and ARR;there was a positive correlation between serum FGF21 level and ARR in NMOSD patients,but there was no significant correlation between FGF21 level in CSF and ARR;the level of FGF21 in CSF of MS patients was negatively correlated with EDSS scores,but there was no significant correlation between the level of FGF21 in serum and EDSS scores;there was no significant correlation between the levels of FGF21 both in serum and CSF and EDSS scores in NMOSD patients.(5)The serum level of FGF2 in patients at relapse and remission stage of MS were significantly higher than those in patients with NMOSD,while FGF21 levels were significantly decreased;however,there was no statistically significant difference in FGF2 and FGF21 levels in CSF between MS patients and NMOSD patients.(6)There was no statistically significant difference in serum FGF2 and FGF21 levels between OB positive and OB negative MS patients;there was no significant difference in serum FGF2 and FGF21 levels between AQP4-Ig G positive and AQP4-Ig G negative NMOSD patients.Conclusion:(1)The serum levels of FGF2 in relapse and remission stage patients of MS and NMOSD were significantly higher than those in the NND group,suggesting that FGF2 may play a role in the pathogenesis of MS and NMOSD.(2)The serum level of FGF2 in MS patients was significantly higher than that in NMOSD patients,suggesting that FGF2 may be more inclined to reflect the level of cellular immune response in the body.(3)The level of FGF21 in CSF of patients with relapse MS was negatively correlated with EDSS scores,suggesting that FGF21 may play a protective role in the pathogenesis of MS.(4)The level of FGF21 in serum of MS patients was significantly lower than that of NMOSD patients and NND patients,and the level of serum FGF21 has no significant difference between NMOSD patients and NND patients,suggesting that FGF21 may be a serological indicator for clinical differentiation between MS and NMOSD.