To investigate the frequency and clinical features of immunoglobulin (Ig) A antibodies against myelin oligodendrocyte glycoprotein (MOG) in patients with central nervous system (CNS) demyelination and healthy controls.

The differential diagnosis of patients with seronegative demyelinating CNS disease is challenging. In this regard, mounting evidence suggests that IgA plays a role in the pathogenesis of different autoimmune diseases. Yet, little is known about the presence and clinical relevance of IgA antibodies against MOG in CNS demyelination.

We conducted an observational, retrospective, longitudinal, multicenter study measuring MOG-IgA in serum using a live cell-based assay. We included a total of 1345 patients with neuromyelitis optica spectrum disorder (NMOSD), other CNS demyelinating diseases, and multiple sclerosis (MS), as well as healthy controls (HC).

Of all patients double-seronegative for MOG-IgG and AQP4-IgG (84%), isolated MOG-IgA was identified in 6% of patients with NMOSD, in 2% of patients with other CNS demyelinating diseases, and in 1% of patients with MS but in none of the HC. The most common disease manifestation in MOG-IgA seropositive patients was myelitis, followed by more frequent brainstem syndrome (p=0.047), and infrequent manifestation of ON (p=0.02) compared to MOG-IgG patients. Among patients fulfilling 2017 McDonald criteria for MS, MOG-IgA was associated with less frequent occurrence of type II oligoclonal bands (OCBs) compared to MOG-IgG/IgA seronegative MS patients (p<0.0001). Further, events of demyelination in MOG-IgA positive patients were more often preceded by infections and/or vaccinations than in MOG-IgG patients. 

We identified MOG-specific antibodies of the IgA isotype in a distinct subgroup of patients, suggesting MOG-IgA as a novel diagnostic biomarker for patients with AQP4-IgG and MOG-IgG double-seronegative CNS demyelination.