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Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis

Department of Neurology, University Hospital, Linköping, Sweden, margarita.callander{at}lio.se

S. Haghighi

Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gothenburg, Sweden

A.-M. Landtblom

Division of Neurology, University Hospital, Linköping, Sweden

C.E. Ahlgren

Sahlgrenska University Hospital, Gothenburg, Sweden

S.I. Nilsson

Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden

L. Rydberg

Department of Transplantation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

H. Al Khoury

Division of Neurology, University Hospital, Linköping, Sweden

L. Rosengren

Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gothenburg, Sweden

O. Andersen

Gothenburg University, Gothenburg, Sweden

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic. Multiple Sclerosis 2007; 13: 441-445. http://msj.sagepub.com

Key Words: genetic susceptibility • HLA • multiple sclerosis • multiple sclerosis trait

Multiple Sclerosis, Vol. 13, No. 4, 441-445 (2007)
DOI: 10.1177/1352458506070264


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