Neuromyelitis Optica Spectrum Disorder With Common Non-organ-specific Autoantibodies

Background:Neuromyelitis optica spectrum disorder (NMOSD) is an infrequent severe demyelinating disease of the central nervous system (CNS), mostly presenting with acute onset and affecting optic nerve and spinal cord but has kaleidoscopic potential clinical and imaging manifestations. It has high recurrence rate and no distinct remission between recurrences, thus would progress fast and result in unrecoverable disability. As its specific autoantibody, AQP4-IgG defines NMOSD as an autoimmune disease dominated by humoral immunity and thus distinct from multiple sclerosis. As the study of NMOSD progressed, it was found that NMOSD may coexist with other autoimmune diseases (Sjogren’s syndrome, Systemic lupus erythematosus, rheumatoid arthritis, etc), or accompany with non-organ-specific autoantibodies seropositive besides AQP4-IgG, which indicated that NMOSD has some potential correlation with other autoimmune diseases or non-organ-specific autoantibodies. Non-organ-specific autoantibodies usually can be found in patients with autoimmune diseases, and target on related structures systemically, not just on certain organs or structures. Common non-organ-specific autoantibodies mainly include antinuclear antibody (ANA), anti-extractable nuclear antigen antibodies (ENA), anti-dsDNA antibody and anti-neutrophil cytoplasmic antibody (ANCA), etc. However, in the clinical practice, other autoimmune diseases accompanied with NMOSD have lower rates of diagnosis, while non-organ-specific autoantibodies are more common and easily tested.Objective:The purposes of this study are to investigate the prevalence of non-organ-specific autoantibodies in NMOSD patients, to compare the clinical features between NMOSD with and without common non-organ-specific autoantibodies, and to explore the influence of non-organ-specific autoantibodies on the clinical mechanism of NMOSD.Methods:Our database comprised 36 patients with NMOSD from January,2013 to February, 2016 who were diagnosed and admitted in the neurology department of Shandong Provincial Hospital. NMOSD patients corresponded to diagnosis criteria for NMOSD in 2007 or the international consensus diagnostic criteria for NMOSD in 2015. Patients who unqualified with the above criteria were excluded. All the patients underwent detailed medical history inquiry and physical examination. Cerebrospinal fluid (CSF) examination, serological examination, and magnetic resonance imaging (MRI) for brain and spinal cord were performed. All the NMOSD patients were divided by non-organ-specific autoantibodies into two groups:the positive group (26 cases) and the negative group (10 cases). The clinical, demographic, laboratory and imaging features between the two groups were retrospective analyzed and the differences were compared.Results:(1) In this study,72.22%(26/36) NMOSD patients were at least one common non-organ-specific autoantibodies positive, and 36.11%(13/36) NMOSD patients were at least two common non-organ-specific autoantibodies positive. ANA (63.89%), anti-SSA antibody (27.78%) and anti-Ro52 antibody (22.22%) were the main non-organ-specific autoantibodies in NMOSD patients.(2) Females were the majority (83.33%), and no difference was found in gender ratio (P> 0.05). NMOSD patients with non-organ-specific autoantibodies were older than those without, and tend to coexist with non-organ-specific autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis) or tumors (glioma, thyroid tumors) more frequently.(3) No statistical differences of clinical manifestations between the two groups (P> 0.05). Sensory deficit, motor deficit and visual impairment were the most common clinical manifestations. Intractable hiccup and nausea (IHN) is a relatively rare but specific symptom of NMOSD, and tend to presented as initial symptom. As initial symptoms, the optic neuritis/myelitis ratio in NMOSD patients with non-organ-specific autoantibodies was lower than those without.(4) The pressure, concentration of protein in cerebrospinal fluid were higher in patients with non-organ-specific autoantibodies (P< 0.05).(5) The difference of lesion distributions between the two groups wasn’t statistical significant.19 out of 26 NMOSD patients in the positive group had spinal cord lesions with 7.32±5.00 segments, while 9 out of 10 NMOSD patients in the negative group had spinal cord lesions with 5.44±3.09 segments, but the difference was not statistically significant (P> 0.05).Conclusions:NMOSD patients with non-organ-specific autoantibodies have more severe inflammation in the central nervous system, and could coexist with non-organ-specific autoimmune diseases and tumors more frequently than those without.