Study On The Correlation Between Serum Level Of Semaphorin3A Protein And The Clinical Features Of Neuromyelitis Optica Spectrum Disorders

Background and purposeNeuromyelitis optica(NMO)(also known as Devic disease)is an immunemediated inflammatory demyelinating disease,mainly characterized by recurrent episodes of optic neuritis and acute transverse myelitis.Although NMO was once thought to be a subtype of multiple sclerosis(MS),the discovery in 2004 of a highly specific serum autoantibody(AQP4-IgG)against astrocytic water channel protein aquaporin-4(AQP4)suggested that NMO is an independent disease entity.In 2007,Wingerchuk et al.first proposed the concept of neuromyelitis optica spectrum disorders(NMOSD)and introduced into individuals who did not meet the diagnostic criteria of NMO,such as AQP4-IgG positive patients with recurrent optic neuritis or with other coexisting autoimmune diseases.According to the new diagnostic criteria in 2015,NMOSD is composed of six core clinical features and produces atypical neuroimaging that further broaden the concept of NMO.NMOSD is more common in Asian populations.It often occurs in young adults and has a high prevalence of relapse and disability.Semaphorins were first discovered in 1990 s as axon guidance molecules,which can provide chemorepellent or chemoattractant signals in the nervous system.Semaphorins are a large and diverse family of proteins,and there are more than 20 types of semaphorins that have been observed.Semaphorin3A(Sema3A)was the first semaphorin found in vertebrates in 1993.Sema3 A is a secreted protein expressed on many immune cells,including dendritic cells,macrophages,B and T cells,but is mainly expressed on regulatory T cells(Tregs),suppressing effector T cell proliferation and pro-inflammatory cytokines secretion.Furthermore,there is a view that Sema3 A has a prominent role in the regulation of the immune system and may participate in the pathogenesis of autoimmune demyelinating diseases of the central nervous system.In the study,the serum Sema3 A level in NMOSD patients was measured,and the relationship between the Sema3 A level and the number of NMOSD recurrence,EDSS scores,CSF leukocyte number,and IgG index was analyzed.The role of serum Sema3 A in the pathogenesis of NMOSD and its relationship with disease prognosis were explored.Methods:The serum samples of NMOSD patients(42 patients)admitted to Department of Neurology of the First Affiliated Hospital of Zhengzhou University from October 2015 to December 2017 were collected,including 5 cases of bilateral optic neuritis(BON),22 cases of optic neuromyelitis(NMO),11 cases of long-segment transverse myelitis,brainstem encephalitis 2 cases,and area postrema syndrome 2 cases.The serum samples of NMOSD patients were collected from acute and remission period,respectively.There were 29 patients with other non-inflammatory neurological disorders(ONND).37 healthy volunteers(HC)were collected as the healthy control group during the same period in our hospital.Using enzyme linked immunosorbent assay(ELISA)to determine the serum Sema3 A levels.Data were analyzed using SPSS 21.0 software.Results:1.Comparison of serum Sema3 A levels between NMOSD group,ONND group and HC groupNMOSD group serum Sema3 A level of acute phase was 4.29±2.27 ng/ml,the remission period serum Sema3 A level was 5.56±2.73 ng/ml,ONND group serum Sema3 A level was 6.39±2.28 ng/ml,HC group serum Sema3 A level was 6.96±3.17 ng/ml.Serum Sema3 A levels in the NMOSD group of acute phase were significantly lower than the NMOSD remission group,ONND group,and HC group(p<0.05,p<0.05,p<0.01).2.Relationship between serum Sema3 A level and cerebrospinal fluid leukocyte number in NMOSD acute groupIn this group of 42 patients with NMOSD,31 cases completed lumbar puncture,and improved CSF routine,immunological testing.The serum Sema3 A level in the normal leukocyte number group was 5.12±2.33 ng/ml,and in the elevated leukocyte number group was 3.26±2.37 ng/ml;The serum Sema3 A level in the elevated leukocyte number group was statistically lower than the normal leukocyte number group(p=0.04).3.Relationship between serum Sema3 A levels and immune indexes in cerebrospinal fluid in NMOSD acute groupThirty-one patients were divided according to the CSF IgG index.The serum Sema3 A level in the normal IgG index group was 4.97±2.64 ng/ml,and the serum Sema3 A level in the elevated IgG index group was 3.09±1.67 ng/ml;the serum Sema3 A level in the elevated IgG index group was significantly lower than the IgG index normal group(p=0.029).4.Relationship between serum Sema3 A level and EDSS score in NMOSD acute phaseIn patients with acute NMOSD,the serum Sema3 A level was 5.18±2.40ng/ml in EDSS<5 score group;the serum Sema3 A level was 3.74±2.05ng/ml in EDSS ≥5 score group;the serum Sema3 A level in EDSS<5 score group was statistically higher than that of EDSS ≥5 score group(p=0.044).5.The relationship between the serum level of Sema3 A and the number of recurrence in NMOSD acute groupIn the NMOSD acute group,the serum Sema3 A level was 3.37±1.71ng/ml in the relapse frequency≥3 group,and the serum Sema3 A level was 4.91±2.43ng/ml in the relapse frequency<3 group;serum Sema3 A level in the relapse frequency≥3 group was statistically lower than in the group of relapse frequency<3 times(p=0.03).Conclusion:1.Serum Sema3 A levels in patients with NMOSD acute phase were significantly lower than those in other groups.Serum Sema3 A levels were lower in CSF elevated leukocyte number group and in elevated IgG index group.It is speculated that Sema3 A may participate in the pathogenesis of NMOSD.2.The serum Sema3 A levels in the NMOSD patients with acute EDSS score ≥ 5 and the number of relapses≥3 groups were lower,suggesting that serum Sema3 A levels may be related to disease severity and recurrence times in the NMOSD.