Abstract General Information


MOG-IgA characterizes a subgroup of patients with central nervous system demyelination


Introduction: The differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, mounting 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 and associated clinical features of MOG-IgA in a cohort of patients with demyelinating CNS disease and healthy participants.

Design/Methods: We conducted an observational, retrospective, longitudinal, multicenter study measuring MOG-IgA in serum using a live cell-based assay. We included 1339 patients with neuromyelitis optica spectrum disorder (NMOSD), other CNS demyelinating diseases, and multiple sclerosis (MS), as well as healthy controls (HC).
Results: Of included isolated MOG-IgA patients, 61% (n=11/18) were females and median age was 31.5 years (range: 3-76). Among patients double-seronegative for AQP4-IgG and MOG-IgG (n=1126/1339; 84%), isolated MOG-IgA was identified in 6% (n= 3/50) of patients with NMOSD, in 2% (n=5/228) of patients with other CNS demyelinating disease, and in 1% (n=10/848) of patients with multiple sclerosis (MS) but in none of the HC (n=0/110). The most common disease manifestation in isolated MOG-IgA seropositive patients was myelitis (65%, n=11/17), followed by more frequent brainstem syndrome (44%, n=7/16; p=0.05 [0.048]), and infrequent manifestation of ON (27%, n=4/15; p=0.02) compared to MOG-IgG patients. Among patients fulfilling 2017 McDonald criteria for MS, MOG-IgA was associated with less frequent type II oligoclonal bands (OCBs) (38%, n=3/8) compared to MOG-IgG/IgA seronegative MS patients (93%, n=325/351; p<0.0001). Further, most patients with isolated MOG-IgA presented events of demyelination after recent infection/vaccination (64%, n=7/11).

Conclusion and relevance: We identified MOG-specific IgA in a subgroup of AQP4-/MOG-IgG double-seronegative patients, suggesting MOG-IgA as a novel diagnostic biomarker for patients with CNS demyelination.




Ana Beatriz Ayroza Galvão Ribeiro Gomes, Ana Beatriz Ayroza Galvão Ribeiro Gomes, Laila Kulsvehagen, Laila Kulsvehagen, Patrick Lipps, Patrick Lipps, Alessandro Cagol, Alessandro Cagol, Nuria Cerdá-Fuertes, Nuria Cerdá-Fuertes, Tradite Neziraj, Tradite Neziraj, Julia Flammer, Julia Flammer, Jasmine Lerner, Jasmine Lerner, Anne-Catherine Lecourt, Anne-Catherine Lecourt, Nina de Oliveira S. Siebenborn, Nina de Oliveira S. Siebenborn, Rosa Cortese, Rosa Cortese, Sabine Schaedelin, Sabine Schaedelin, Vinicius Andreoli Schoeps, Vinicius Andreoli Schoeps, Aline de Moura Brasil Matos, Aline de Moura Brasil Matos, Natalia Trombini Mendes, Natalia Trombini Mendes, Clarissa dos Reis Pereira, Clarissa dos Reis Pereira, Mario Luiz Ribeiro Monteiro, Mario Luiz Ribeiro Monteiro, Samira Luisa dos Apostolos Pereira, Samira Luisa dos Apostolos Pereira, Patrick Schindler, Patrick Schindler, Claudia Chien, Claudia Chien, Carolin Schwake, Carolin Schwake, Ruth Schneider, Ruth Schneider, Thivya Pakeerathan, Thivya Pakeerathan, Orhan Aktas, Orhan Aktas, Urs Fischer, Urs Fischer, Mattias Mehling, Mattias Mehling, Tobias Derfuss, Tobias Derfuss, Ludwig Kappos, Ludwig Kappos, Ilya Ayzenberg, Ilya Ayzenberg, Marius Ringelstein, Marius Ringelstein, Friedemann Paul, Friedemann Paul, Dagoberto Callegaro, Dagoberto Callegaro, Jens Kuhle, Jens Kuhle, Athina Papadopoulou, Athina Papadopoulou, Cristina Granziera, Cristina Granziera, Anne-Katrin Pröbstel, Anne-Katrin Pröbstel