Distribution of HLA class II alleles among Scandinavian patients with systemic lupus erythematosus (SLE): an increased risk of SLE among non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes?

HLA-DRB1, -DRB3, -DQA1 and -DQB1 alleles were determined by DNA typing in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 129 controls. DRB103,DRB30101,DQA10501,DQB10201 were significantly increased in the patient group, with relative risks (RR) of 2.80, 3.07, 3.55 and 2.12, respectively. These alleles are in strong linkage disequilibrium, and their possible relative contributions in predisposition to SLE are difficult to distinguish. The strongest association was found for DQA10501, which is in linkage disequilibrium with DRB103 as well as DRB111,12 (DR5). An increased frequency of DRB111,12 was observed (RR = 1.89, ns). No association with DRB115,16 (DR2) was found. The patients had a higher frequency of HLA class II homozygosity than the controls (RR = 5.05, p = 0.0005). When compared to the low-risk group (nonDRB103 class II heterozygotes), the cases homozygous for DRB103,DQA10501,DQB10201, known to be in linkage disequilibrium with the complement allele C4AQ0, had the highest relative risk of developing SLE (RR = 16.39, p = 0.0002). However non[DRB103,DQA10501,DQB10201] class II homozygotes had a higher relative risk (RR = 4.68, p = 0.0147) than DRB103,DQA10501,DQB10201 heterozygotes, known to carry the C4A*Q0 allele (RR = 2.72, p = 0.0088). This may suggest that HLA class II molecules are directly involved in susceptibility to SLE.