Genetic determinants of antibody levels in cerebrospinal fluid in multiple sclerosis: Possible links to endogenous retroviruses

Abstract

The pathogenesis ofmultiple sclerosis (MS) has not been clarified. In addition to environmental factors; genetic determinants have been implicated in the pathogenesis ofMS. Furthermore, endogenous retroviruses (ERV)might play a role inMS. The presence of oligoclonal immunoglobulin in cerebrospinal fluid (CSF) is a typical feature ofMS. Recently, genetic polymorphisms in loci on human chromosomes 6, 14 and 18 have been identified as major determinants of CSF antibody levels inMS. The functional relevance of these single nucleotide polymorphisms (SNPs) remains unclear and none of them is located in an open reading frame. In previous studies, we identified ERV sequences in the vicinity of MS associated SNPs. Here, we describe the identification of ERV sequences in the neighborhood of SNPs associated with CSF antibody levels. All of the identified SNPs are located in the vicinity of ERV sequences. One of these sequences has very high homology to a sequence derived from the so-called MS-associated retrovirus (MSRV). Another cluster of three ERV sequences from the immunoglobulin heavy chain locus has retained the typical organization of retroviral genomes. These observations might shed new light on a possible association between ERVs andMS pathogenesis.