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Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients

Journal article
Authors Sara Haghighi
Annika Lekman
Staffan Nilsson
Maria K. Blomqvist
Oluf Andersen
Published in Journal of the Neurological Sciences
Volume 326
Issue 1-2
Pages 35-39
ISSN 0022-510X
Publication year 2013
Published at Institute of Neuroscience and Physiology
Department of Mathematical Sciences, Mathematical Statistics
Pages 35-39
Language en
Links dx.doi.org/10.1016/j.jns.2013.01.00...
Keywords Multiple sclerosis, Glycosphingolipids, Antibodies, Cerebrospinal fluid, Siblings, Endophenotypes, cerebrospinal-fluid, 1st-degree relatives, risk-factors, cells, ms, immunopathy, disorders, responses
Subject categories Neurology

Abstract

A proportion of healthy siblings of multiple sclerosis (MS) patients have an oligodonal immunological reaction in their cerebrospinal fluid (CSF) termed the "MS oligoclonal trait". The CSF levels of the major myelin glycosphingolipid sulfatide and serum antibodies against the glycosphingolipids sulfatide and galactosylceramide were recently reported to be increased in MS patients. We studied the levels of these substances in pairs of 46 patients and their 46 healthy siblings and 50 unrelated healthy blood donors (HBD). The sulfatide concentration in CSF was assayed by thin layer chromatography and immunostaining, and the concentration of galactosylceramide by densitometry after thin layer chromatography. Anti-glycosphingolipid antibody levels were assayed by ELISA. In the healthy siblings, the CSF sulfatide concentrations were markedly increased (p<0.001, age adjusted p = 0.025), and the serum IgM anti-GalCer antibodies were increased in healthy siblings compared with HBD (p = 0.02). The increased sulfatide or antibody levels did not co-segregate with the "MS oligoclonal trait" or the HLA-DR15 phenotype. In conclusion, a proportion of healthy siblings of MS patients have increased CSF sulfatide and anti-glycosphingolipid antibody levels, which may, analogous to the "MS oligoclonal trait", constitute an "MS glycosphingolipid endophenotype". Endophenotypes could potentially simplify the genetics of complex disorders

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