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Anti--glucose–based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event

University of Ottawa, The Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 mfreedman{at}ottawahospital.on.ca

J Laks

University of Ottawa, The Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6

N Dotan

Glycominds Ltd, 1 Yodfat St, Alon Bldg, Lod 71291, Israel

RT Altstock

Glycominds Ltd, 1 Yodfat St, Alon Bldg, Lod 71291, Israel

A Dukler

Glycominds Ltd, 1 Yodfat St, Alon Bldg, Lod 71291, Israel

CJM Sindic

Cliniques Universitaires Saint-Luc, UCL, 1200 Brussels, Belgium

Background

There is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (RRMS).

Objective

We investigated whether levels of IgM antibodies to Glc(1,4)Glc() (GAGA4) or to a panel of four glucose-based glycans could differentiate MS from other neurological diseases (OND) or predict risk of early relapse following first presentation (FP) of RRMS.

Methods

Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n = 44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100). Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and cohort-B. Cohort-C IgM antibodies to glucose-based glycan panel were measured by immunofluorescence.

Results

FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P = 0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97% for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58 patients experienced early relapse (<24 months), 31 had late relapse (24 months), and 11 did not experience second attack during follow-up. Kaplan–Meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (P = 0.02, log rank).

Conclusions

Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher levels of serum anti--glucose IgM in FP patients predict imminent early relapse.

Key Words: antibodies • anti-glucose antibodies • anti-glycan antibodies • biomarker • diagnosis • enzyme immunoassay • IgM • multiple sclerosis • prognosis

Multiple Sclerosis, Vol. 15, No. 4, 422-430 (2009)
DOI: 10.1177/1352458508101944


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