Absence of DRwl5/3 and of DRwl5/7 heterozygotes in Caucasian patients with systemic lupus erythematosus

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Abstract
Polymorphic MHC class II molecules determine immune responsiveness towards pathogens and also contribute to susceptibility or resistance to a number of different autoimmune diseases, including systemic lupus erythematosus (SLE). The HLA-DR and -DQ alleles of 52 patients with SLE were analyzed by serology and, for 42 patients, HLA-DRB1, -B3 and DQB1 allelic polymorphism was determined by oligotyping on PCR-amplified DNA. While we confirm the increase of DR3 (44.2% versus 16% in controls; p less than 0.001) reported by others, we observed a complete absence of DRw15(2)/DR3 and DRw15(2)/DR7 heterozygotes among Caucasian patients. Moreover HLA-DQB1 oligotyping revealed the absence of DQB1*0602/0201 heterozygotes in our panel of Caucasoid SLE patients. Since both DR3 and DR7 haplotypes share the same DQB1*0201-encoded DQ beta chain, and since DRw15 is known to be in linkage disequilibrium with DQA1*0102, it can be predicted that DQA1*0102/DQB1*0201 combinations are absent in Caucasian patients. We therefore propose that a DQA1*0201/DQB1*0201-encoded HLA-DQ trans-dimer formed in these heterozygotes might function as a suppressor-inducer molecule that confers resistance against SLE.