Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination
Authors: Ayroza Galvão Ribeiro Gomes Ana Beatriz , Kulsvehagen Laila , Lipps Patrick , Cagol Alessandro , Cerdá-Fuertes Nuria , Neziraj Tradite , Flammer Julia , Lerner Jasmine , Lecourt Anne-Catherine , de Oliveira S. Siebenborn Nina , Cortese Rosa , Schaedelin Sabine , Andreoli Schoeps Vinicius , de Moura Brasil Matos Aline , Trombini Mendes Natalia , dos Reis Pereira Clarissa , Ribeiro Monteiro Mario Luiz , dos Apóstolos-Pereira Samira Luisa , Schindler Patrick , Chien Claudia , Schwake Carolin , Schneider Ruth , Pakeerathan Thivya , Aktas Orhan , Fischer Urs , Mehling Matthias , Derfuss Tobias , Kappos Ludwig , Ayzenberg Ilya , Ringelstein Marius , Paul Friedemann , Callegaro Dagoberto , Kuhle Jens , Papadopoulou Athina , Granziera Cristina , Pröbstel Anne-Katrin 
Published: August 2023

ImportanceDifferential 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.ObjectiveTo investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls.Design, Setting, and ParticipantsThis 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 MeasuresFrequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG.ResultsAfter 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 &amp;lt; .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 RelevanceIn 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.