Human Autoantibodies Against MOG Isoforms α3 Antibodies Suggest Relapsing Disease Course in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

초록

Background and Objectives A proportion of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) experience relapses, but biomarkers predicting which patients are likely to relapse are not yet widely available. The MOG alpha 1 isoform is the most commonly used in diagnostic MOG antibody assays, while the clinical relevance of antibodies against other MOG isoforms remains unclear. Methods This study used a stepwise approach using international multicenter serum samples collected prospectively. First, diagnostic accuracy of the MOG alpha 1 and beta 1 isoforms was compared using 748 consecutive sera from Korean patients suspected of having demyelinating disease of the CNS. Next, the predictive values of antibodies against each of 7 MOG isoforms for relapses were assessed on sera from Korean patients with MOGAD (derivation cohort). Finally, the association between MOG isoform antibody with relapses was validated in 2 independent cohorts: a Korean validation cohort (n = 49) and a UK validation cohort (n = 56). Results Both MOG alpha 1 antibody and MOG beta 1 antibody assays had comparable diagnostic accuracy. Among patients with MOGAD, the presence of MOG alpha 3 antibody was associated with a higher risk of relapse, with a hazard ratio of 4.3 in the derivation cohort (log-rank p < 0.001). This finding was also confirmed in an independent smaller Korean validation cohort (log-rank p = 0.009) and in a subgroup of UK validation cohort (log-rank p = 0.048). Discussion The presence of MOG alpha 3-IgG in patients with MOGAD may be associated with an increased risk of relapse, indicating that early preventive treatment strategies may be appropriate in these individuals. MOG beta 1-IgG demonstrated diagnostic accuracy similar to MOG alpha 1-IgG.C lassification of Evidence This study provides Class II evidence that MOG alpha 1 antibody and MOG beta 1 antibody assays have comparable diagnostic accuracy for MOGAD.