Clinical and immunological differences between MOG associated disease and anti AQP4 antibody-positive neuromyelitis optica spectrum disorders: Blood-brain barrier breakdown and peripheral plasmablasts.

BACKGROUND: Patients with anti-aquaporin-4 (AQP4) water channel antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) associated disease (MOGAD) often present with similar clinical symptoms, and some cases are hard to differentiate at the time of onset. In this study, we compared the clinical characteristics, cerebrospinal fluid (CSF) analysis parameters, and peripheral T/B lymphocyte subsets during the active and chronic phases in AQP4-NMOSD and MOGAD. METHODS: A total of 17 MOGAD cases and 24 AQP4-NMOSD cases were studied. The clinical characteristics in both groups were summarized, including disease duration, total number of attacks, lesions, prevention of relapse during remission, and CSF analysis results during the active phase. T/B lymphocyte subsets were further investigated in the active and chronic phases. RESULTS: In the comparative study on clinical symptoms, a large proportion of optic neuritis was unilateral in MOGAD. In the comparative study on CSF analysis, protein level was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.006); myelin basic protein was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.04); albumin quotient was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.02); and IgG Quotient was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.05). In the analysis of T/B lymphocyte subsets, plasmablasts of the B cell subset in the active phase were significantly lower in MOGAD (2.1 ± 2.4) compared to AQP4-NMOSD (7.8 ± 7.2) (p < 0.05). In the chronic phase, transitional B cells were significantly higher in MOGAD (2.1 ± 1.8) compared to AQP4-NMOSD (0.6 ± 0.4) (p < 0.01). CONCLUSION: Clinical characteristics of MOGAD were similar to those of AQP4-NMOSD, but increased blood brain barrier permeability was suggested to be less severe in MOGAD compared to AQP4-NMOSD from CSF analysis. Furthermore, the pathogenesis of the two diseases was clearly distinct as plasmablasts in the active phase were not elevated in MOGAD, but were increased in AQP4-NMOSD.

Tacrolimus is effective for neuromyelitis optica spectrum disorders with or without anti-AQP4 antibody.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory central nervous system disorders characterized by optic neuritis, transverse myelitis, and anti-aquaporin 4 (AQP4) antibody production. However, it has recently been shown that some cases of typical NMOSD can be anti-AQP4 antibody-negative as well. In this study, we retrospectively investigated the disorder relapse-suppressing effect of tacrolimus (TAC) when combined with prednisolone (PSL) in anti-AQP4 antibody-positive and -negative NMOSD cases. METHODS: Subjects were NMOSD outpatients treated at our hospital in August 2016 who fulfilled the 2015 International Panel for NMO Diagnosis criteria and whose medical history before visiting our department was known; anti-myelin oligodendrocyte glycoprotein antibody-positive cases were excluded. We retrospectively investigated the annualized relapse rate (ARR) before and after combined TAC and PSL treatment in 50 NMOSD cases who had been using TAC with PSL for at least 1 year and whom we were also able to observe. RESULTS: There were 42 anti-AQP4 antibody-positive cases and 8 negative cases. Observation periods of the anti-AQP4 antibody-positive cases were 1.1 years before TAC and 5.1 years after TAC. ARR before TAC was 1.0 and 0.08 after TAC, indicating a relapse-suppression rate of 92% (p < 0.001) and clear improvement. In the anti-AQP4 antibody-negative group, the observation period was 5.6 years before and 4.1 years after TAC. ARR before TAC was 0.5 and 0.07 after TAC. The relapse-suppression rate was 86% (p < 0.05), which was obviously as effective as in the anti-AQP4 antibody-positive group. PSL dose in the anti-AQP4 antibody-positive group was 15.0 mg/day at the start of TAC and was reduced to 6.3 mg/day after 2 years (p < 0.001). The Expanded Disability Status Scale (EDSS) score decreased from 4.5 at the start of TAC to 2.0 after 2 years in the anti-AQP4 antibody-positive group (p < 0.05), which was a clear improvement. CONCLUSION: Combined use of TAC with PSL clearly suppressed relapse of both anti-AQP4 antibody-positive and -negative NMOSD. In the anti-AQP4 antibody-positive group, both PSL dose and EDSS score decreased compared with the dose at the start of the study.