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

From Journal of Allergy and Clinical Immunology Volume 116, Issue 2 , August 2005, Pages 453-459

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 (α-GalC) antibodies in MS and to evaluate them as biomarkers of disease.

Methods
α-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 α-GalC IgG titers between patients with relapsing-remitting (RR)–MS and healthy controls (HCs; P < .001). The frequencies of α-GalC antibody-positive subjects (α-GalC titers ≥ mean HC titers + 3 SD) are also significantly elevated in RR-MS compared with HC (40% vs 0%; P = .0033). Immunoaffinity purified α-GalC IgGs from human serum bind to cultured human oligodendrocytes, indicating that the ELISA detects a biologically relevant epitope. Corroborating these findings, α-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) α-GalC antibodies appear MS-specific and are not found in healthy subjects, unlike antibodies against myelin proteins; (2) when present, α-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.