Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases.

BACKGROUND: We evaluated the seroprevalence of myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG) and associated clinical features of patients from a large adult-dominant unselected cohort with mainly relapsing central nervous system (CNS) inflammatory diseases. We also investigate the clinical relevance of MOG-IgG through a longitudinal analysis of serological status over a 2-year follow-up period. METHODS: Serum samples from 505 patients with CNS inflammatory diseases at the National Cancer Center were analysed using cell-based assays for MOG-IgG and aquaporin-4 immunoglobulin G (AQP4-IgG). MOG-IgG serostatus was longitudinally assessed in seropositive patients with available serum samples and at least 2 years follow-up. RESULTS: Twenty-two of 505 (4.4%) patients with CNS inflammatory diseases were positive for MOG-IgG. Patients with MOG-IgG had neuromyelitis optica spectrum disorder (NMOSD, n=10), idiopathic AQP4-IgG-negative myelitis (n=4), idiopathic AQP4-IgG-negative optic neuritis (n=4), other demyelinating syndromes (n=3) and multiple sclerosis (n=1). No relapses were seen in patients when they became MOG-IgG seronegative, whereas a persistent positive serological status was observed in patients with clinical relapses despite immunotherapy. CONCLUSIONS: In a large adult-predominant unselected cohort of mainly relapsing CNS inflammatory diseases, we confirmed that NMOSD phenotype was most commonly observed in patients with MOG-IgG. A longitudinal analysis with 2-year follow-up suggested that persistence of MOG-IgG is associated with relapses.

Neutralizing Antibodies Against Interferon-Beta in Korean Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-ß) can develop neutralizing antibodies (NAbs) against IFN-ß that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-ß in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-ß for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-ß-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-ß-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-ß-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-ß.