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| Item Type: | Article |
|---|---|
| Title: | Immunoglobulin A antibodies against myelin oligodendrocyte glycoprotein in a subgroup of patients with central nervous system demyelination |
| Creators Name: | Ayroza Galvão Ribeiro Gomes, A.B., Kulsvehagen, L., Lipps, P., Cagol, A., Cerdá-Fuertes, N., Neziraj, T., Flammer, J., Lerner, J., Lecourt, A.C., de Oliveira S Siebenborn, N., Cortese, R., Schaedelin, S., Andreoli Schoeps, V., de Moura Brasil Matos, A., Trombini Mendes, N., Dos Reis Pereira, C., Ribeiro Monteiro, M.L., Dos Apóstolos-Pereira, S.L., Schindler, P., Chien, C., Schwake, C., Schneider, R., Pakeerathan, T., Aktas, O., Fischer, U., Mehling, M., Derfuss, T., Kappos, L., Ayzenberg, I., Ringelstein, M., Paul, F., Callegaro, D., Kuhle, J., Papadopoulou, A., Granziera, C. and Pröbstel, A.K. |
| Abstract: | IMPORTANCE: Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. OBJECTIVE: To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. MAIN OUTCOMES AND MEASURES: Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. RESULTS: After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P = .048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P = .02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P < .001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). CONCLUSION AND RELEVANCE: In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination. |
| Keywords: | Aquaporin 4, Autoantibodies, Brain Stem, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Longitudinal Studies, Multiple Sclerosis, Myelin-Oligodendrocyte Glycoprotein, Neuromyelitis Optica / Diagnosis |
| Source: | JAMA Neurology |
| ISSN: | 2168-6149 |
| Publisher: | American Medical Association |
| Volume: | 80 |
| Number: | 9 |
| Page Range: | 989-995 |
| Date: | September 2023 |
| Official Publication: | https://doi.org/10.1001/jamaneurol.2023.2523 |
| PubMed: | View item in PubMed |
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