Potential New Biomarker for CNS Demyelination Identified

Results from a study recently published in JAMA Neurology identified myelin oligodendrocyte glycoprotein (MOG)-associated immunoglobulin A (IgA) in a small number of patients who were double negative for serum aquaporin 4 (AQP4)-IgG and MOG-IgG. The findings suggest that MOG-IgA may be a potential biomarker for central nervous system (CNS) demyelination.

The longitudinal study included a discovery cohort comprising 1339 patients with multiple sclerosis (MS) (n=865), neuromyelitis optica spectrum disorder (NMOSD) (n=196), or MOG antibody-associated disease (n=278), and a confirmation cohort comprising 110 healthy control participants. Participant serum and cerebrospinal fluid (CSF) samples were assessed using a cell-based assay.

Of the patients who were double-seronegative for AQP4-/MOG-IgG (n=1126), 1.6% had isolated seropositivity for MOG-IgA. These individuals comprised 1% of the patients with MS, 6% of the patients with NMOSD, and 2% of the patients with other demyelinating diseases. Researchers compared statistical differences in disease manifestation, showing that patients with isolated MOG-IgA seropositivity showed higher rates of myelitis and brainstem syndrome, but lower rates of optic neuritis. Isolated MOG-IgA seropositive patients showed lower rates of CSF-specific oligoclonal bands (OCBs) in imaging, compared to MOG-IgA/-IgG seronegative patients with MS, and they presented with one of the following imaging features: myelitis, periventricular lesion, tumefactive deep white matter lesion, and brainstem lesion. The identification of MOG-specific IgA in a subgroup of patients double-seronegative for AQP4-/MOG-IgG with distinct imaging features and disease manifestations suggests the potential of IgA as a biomarker for CNS demyelinating disease.

The study authors noted that the small number of patients seropositive for isolated IgA serves as a limitation for the conclusions drawn from the results. They state that future research is needed to fully explore and characterize underlying pathogenic mechanisms and the clinical relevance of MOG-IgA.