Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis

Background: Galactocerebroside, the major glycolipid of central nervous system myelin, is a known target for pathogenic demyelinating antibody responses in experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). Objective: To address the importance of anti-galactocerebroside (alpha-GalC) antibodies in MS and to evaluate them as biomarkers of disease. Methods: alpha-GalC IgGs were quantified from sera of patients with MS and in marmoset EAE by a new immunosorbent assay. Results: We report a significant difference in serum alpha-GalC IgG titers between patients with relapsing-remitting (RR)-MS and healthy controls (HCs; P < .001). The frequencies of alpha-GalC antibody-positive subjects (alpha-GalC titers >= mean HC titers + 3 SD) are also significantly elevated in RR-MS compared with HC (40% vs 0%; P = .0033). Immunoaffinity purified alpha-GalC IgGs from human serum bind to cultured human oligodendrocytes, indicating that the ELISA detects a biologically relevant epitope. Corroborating these findings, alpha-GalC antibody responses in marmoset EAE were similarly found to be specifically associated with the RR forms and not the peracute or progressive forms, in contrast with other anti-myelin antibodies (P = .0256). Conclusion: (1) alpha-GalC antibodies appear MS-specific and are not found in healthy subjects, unlike antibodies against myelin proteins; (2) when present, alpha-GalC antibodies identify mostly RR-MS and may be an indicator of ongoing disease activity. This novel assay is a suitable and valuable method to increase accuracy of diagnosis and disease staging in MS.