Human autoantibodies against MOG isoforms: α3 antibodies suggest relapsing disease course in MOGAD

초록

Introduction: There is a need for biomarkers to help predict relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) after their first attack. MOGα1 is the standard isoform for MOG-IgG diagnostic testing, while the relevance of antibodies against other isoforms of MOG in predicting relapses remains unclear. Objectives/Aims: This study aimed to explore the clinical value of antibodies against various MOG isoforms in patients with MOGAD, focusing on their diagnostic utility and potential to predict relapse. Methods: We investigated whether the different MOG isoforms were associated with a higher risk of relapses in a stepwise international multicenter retrospective study. Using sera from 748 patients, antibodies against MOG isoforms α1 and β1 were screened, while five additional isoforms (α2, α3, β2, β3, and 5) were analyzed in 58 patients in the derivation cohort with confirmed MOGAD. Validation was performed in two independent cohorts: a national (Korean) cohort (n = 49) and an international (UK) cohort (n = 56). Subgroup analyses were also conducted in patients without long-term oral corticosteroid and non-steroidal immunosuppressant use. Results: MOGβ1-IgG demonstrated diagnostic accuracy comparable to MOGα1-IgG. MOGα3-IgG was associated with a significantly higher risk of relapse, with a hazard ratio of 4.1 in the derivation cohort (p = 0.002) and 3.1 in the national cohort (p = 0.015). However, this association was not observed in the UK cohort, perhaps due to longer corticosteroid use compared to the Korean cohort. Subgroup analyses across cohorts (n = 82) revealed a 2.6-fold increased relapse risk in MOGα3-IgG-positive patients without long-term corticosteroid use over 6 months (p = 0.004). Conclusion: MOGβ1-IgG demonstrated diagnostic accuracy similar to MOGα1-IgG, and MOGα3-IgG was found to be associated with a higher risk of relapse. MOGα3-IgG is a promising biomarker for relapse prediction, and prospective studies addressing treatment confounders should be set up to validate these results.