Characterising a Clinical and Laboratory Patient Profile that Predicts Relapse in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Abstract

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating pathology of the central nervous system (CNS) diagnosed by the detection of antibodies targeting oligodendrocyte-expressed MOG (MOG-IgG). Disease course is monophasic or relapsing and neurological disability accumulates with relapse. Laboratory biomarkers have the potential to predict disease course and activity, thus, ensuring early initiation of immunosuppression in individuals at risk of relapse-associated disability accrual, while minimising unnecessary immunosuppression in monophasic individuals. A challenge of MOGAD research is the rarity of its incidence, often translating to limited sample sizes. For these reasons, we first summarized the literature on biomarkers of prognosis and pathological mechanisms of disease. We then conducted a systematic review with meta-analysis to investigate the capability of laboratory biomarkers to predict disease course, as well as differentiate remission compared to attack disease activity. 106 studies with ≥1710 individuals were included in the systematic review. Relapsing course was associated with persistent seropositivity (OR 2.7 (95%CI 1.8–4.0), p<0.0001), lower likelihood of seroreversion to negative status (HR 0.19 (95%CI 0.14–0.26), p<0.0001), and delayed seroreversion compared to monophasic participants (median 19 years versus 2.5 years, p<0.0001). ADEM was not associated with relapsing course (OR 0.049 (95%CI 0.0029–0.84), p=0.037). Serum MOG-IgG titre – negative, low positive, or clear positive – discriminated disease state. Attack was associated with clear positive titre (OR 3.6 (95%CI 2.6–5.0), p<0.0001), but not negative titre (OR 0.073 (95%CI 0.028–0.19), p<0.0001). CSF leukocytosis (≥5 cells/uL) was associated with attack (OR 3.1 (95%CI 1.7-5.9), p=0.0004). The findings support serial serum MOG-IgG testing at 3-6 month intervals in the first 12 months of disease to assist in relapse risk stratification.