Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Insights into pathogenesis and biomarkers of prognosis

MOG antibody-associated disease (MOGAD), an inflammatory demyelinating pathology, is typically associated with the clinical phenotypes acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), or transverse myelitis (TM). The mainstay of diagnosis is detection of antibodies targeting oligodendrocyte-expressed MOG (MOG-IgG). MOG-IgG-mediated demyelination occurs via complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), enhanced cognate T-cell CNS infiltration and activation, and oligodendrocyte cytoskeleton disruption, but the exact role of the immune system in MOGAD is still poorly understood. The disease course is either monophasic or relapsing, with relapsing course affecting approximately two-thirds of individuals. Neurological disability accumulates with relapse and may manifest as visual, motor, sensory, and cognitive deficits. Thus, accurate disease course prediction is of paramount importance. Prognostic biomarkers, implemented at a global scale, have the potential to guide timely therapeutic decisions to limit relapse-associated disability accrual while simultaneously avoiding unnecessary immunosuppression in monophasic individuals. This review explores recent insights in the understanding of MOGAD pathogenesis as well as advances in prognostic biomarkers of relapsing course and disease activity.