Systemic lupus erythematosus and the extended major histocompatibility complex—evidence for several predisposing loci

Open Access
Publisher Website
Google Scholar
Abstract
Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease reported to be associated with several alleles in the HLA complex. The purpose of this study was to systematically examine the extended HLA complex (xMHC) in order to get an overview of the primary predisposing genetic factors. Materials and methods. One hundred and sixty-four SLE patients and 254 healthy, unrelated controls were genotyped for HLA-DRB1, -B and -A alleles, as well as 13 microsatellites markers covering the xMHC. Moreover, we selected 335 additional controls matched with the patients for the HLA haplotypes showing the strongest associations, in order to look for additional predisposing loci. Results. Two regions of the xMHC showed associations: the region covering DRB1 to B, and the extended class I region. Explicitly, DRB1*03 and B*08 displayed strong associations with SLE, which seem to be independent of each other. Furthermore, associations were seen with alleles at microsatellites D6S2225 and D6S2223, located about 3.6 Mb telomeric of HLA-B, and these were not secondary to the associations found with DRB1*03 and B*08. Conclusion. Both the DRB1*03 and the B*08 alleles display disease association, either implicating involvement of both alleles or caused by another yet unidentified gene(s) in linkage disequilibrium. The associations found in the extended class I region could be markers for a ‘novel’ predisposing locus (loci) in SLE, adding to the risk conferred by DRB1*03 and B*08. Interestingly, this region has been shown to also be associated with other autoimmune diseases, hence the gene(s) might confer a general propensity for autoimmunity.