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 > 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).


CONCLUSIONS
(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.
Menge
Til
T
Department of Neurology, University of California San Francisco, San Francisco, CA 94143-0114, USA.
Lalive
Patrice H
PH
von Büdingen
Hans-Christian
HC
Cree
Bruce
B
Hauser
Stephen L
SL
Genain
Claude P
CP
D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D002144:Callithrix; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology*
D015415:Biomarkers; D005699:Galactosylceramides; D007074:Immunoglobulin G; C002454:galactocerebroside