Human Autoantibodies Against MOG Isoforms: α3 Antibodies Suggest Relapsing Disease Course in Myelin Oligodendrocyte...

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 MOGα1 isoform is the most commonly used in diagnostic MOG antibody assays, while the clinical relevance of antibodies against other MOG isoforms remains unclear.

This study used a stepwise approach using international multicenter serum samples collected prospectively. First, diagnostic accuracy of the MOGα1 and β1 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).

Both MOGα1 antibody and MOGβ1 antibody assays had comparable diagnostic accuracy. Among patients with MOGAD, the presence of MOGα3 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).

The presence of MOGα3-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. MOGβ1-IgG demonstrated diagnostic accuracy similar to MOGα1-IgG.

This study provides Class II evidence that MOGα1 antibody and MOGβ1 antibody assays have comparable diagnostic accuracy for MOGAD.