Beyond Positivity: Understanding and Interpreting MOG-IgG Testing in MOGAD

The diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) relies heavily on detecting serum MOG-IgG by cell-based assay, but seropositivity alone does not establish the disease. In selected clinical cohorts, the positive predictive value of MOG-IgG ranges from approximately 50%-70% at low titers, depending on the assay and cohort, to near 100% at high titers, and inter-laboratory agreement is markedly lower in the low-positive samples than for clearly positive or negative samples. The difficulty in interpreting low-positive MOG-IgG results largely reflects the interplay of two elements: biological factors (including antigen-related background reactivity and potential cross-reactive immunoreactivity) and methodological variability between assays (including differences in antigen presentation, live versus fixed assay platforms, secondary antibody selection, fluorescence readout, sample timing, and locally validated cutoffs). This ambiguity is unlikely to be resolved by assay optimization alone. The 2023 International MOGAD Panel criteria address these issues by requiring stronger clinical and radiological support when the serological evidence is weaker. Accordingly, MOG-IgG should be interpreted as probabilistic evidence within the clinical and MRI context, rather than as a stand-alone diagnostic marker.