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

Abstract

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 > or = 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.

• Authors: Til Menge, Patrice H Lalive, Hans-Christian von Büdingen, Bruce Cree, Stephen L Hauser, Claude P Genain
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 116 Issue 2 Pg. 453-9 (Aug 2005) ISSN: 0091-6749 [Print] United States
• PMID: 16083805 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers
• Galactosylceramides
• Immunoglobulin G
• galactocerebroside

Topics

• Adult
• Aged
• Animals
• Biomarkers
• Callithrix
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Galactosylceramides (immunology)
• Humans
• Immunoglobulin G (blood)
• Immunohistochemistry
• Male
• Middle Aged
• Multiple Sclerosis (diagnosis, immunology)