Clinical Significance Of Anti-neurofascin 155 Antibody In Neuromyelitis Optica Spectrum Disorders

Objective Neuromyelitis optica spectrum disorders(NMOSD)are autoimmune demyelinating diseases in the central nervous system.The main pathological mechanism of NMOSD is thought to be astrocyte damage and demyelination caused by antibody-mediated complement-depended cytotoxicity.Neurofascin 155(NF155)is a cell surface protein mainly expressed at the myelin sheath in the paranode of the node of Ranvier and plays an important role in maintaining the intact structure of the node of Ranvier and normal conduction of nerve impulse.Neurofascin 155 immunoglobulin G(NF155-Ig G)has been found in a variety of autoimmune demyelinating diseases,such as multiple sclerosis(MS),Guillain-Barré syndrome(GBS),chronic inflammatory demyelinating polyneuropathy(CIDP),combined central and peripheral demyelination(CCPD).This study aims to investigate the presence of NF155-Ig G in the serum of NMOSD patients,and to explore the clinical significance of NF155-Ig G in NMOSD.Methods 128 NMOSD patients admitted to Tianjin Medical University General Hospital from July 2010 to July 2019 were recruited.Demographic data,clinical data,imaging data,and serum samples were collected.A cell line stably expressing NF155 was established,and cell-based immunofluorescence assay(CBA)was used to detect NF155-Ig G in serum.The differences in clinical manifestations,laboratory examinations,electromyography results,and imaging characteristics between NF155-Ig G positive and negative patients were compared.Results 1.Among 128 NMOSD patients,18 patients(14.06%)were positive for serum NF155-Ig G.2.The proportion of NMOSD patients with NF155-Ig G positive coexisting with other autoimmune diseases and connective tissue diseases(CTD)was higher than those of NMOSD patients with NF155-Ig G negative(50% vs.5.5%,P < 0.001 and 44.4% vs.4.5%,P < 0.001,respectively).3.Compared with NF155-Ig G negative patients,NF155-Ig G positive patients showed higher positive rates of serum anti-SSA antibodies(71.4% vs.18.7%,P < 0.001),anti-SSB antibodies(28.6% vs.4.4%,P = 0.008),anti-Ro-52 antibodies(71.4% vs.19.8%,P < 0.001)and rheumatoid factor(21.4% vs.3.3%,P = 0.030),and the differences were all statistically significant.4.Abnormalities in distal motor latency(DML)and F-wave latency of median nerve,in F-wave latency of tibial nerve,and in sensory conduction velocity(SCV)of peroneal nerve were higher in patients with NF155-Ig G positive than in patients with NF155-Ig G negative.5.18 NMOSD patients with NF155-Ig G positive were all female.The first symptoms were mainly optic neuritis and acute myelitis.The superficial sensory abnormalities and weakness of the limbs were the most common clinical manifestations.Electromyography of some patients indicated peripheral nerve injury.Conclusions Anti-NF155 antibodies were detected in some patients with NMOSD.The first symptoms of NMOSD patients with NF155-Ig G positive were mainly optic neuritis and acute myelitis.The superficial sensory abnormalities and weakness of the limbs were the most common clinical manifestations.Compared with patients with NF155-Ig G negative,electromyography of some patients with NF155-Ig G positive suggested higher proportions of prolongation of DML and F-wave latencies and the decrease in SCV.The proportion of coexisting with other autoimmune diseases and CTD,the positive rates of serum anti-SSA antibodies,anti-SSB antibodies,anti-Ro-52 antibodies,and rheumatoid factors were higher in NMOSD patients with NF155-Ig G positive than those with NF155-Ig G negative.NMOSD patients with NF155-Ig G positive may be more prone to coexisting with autoimmune-related diseases.