Opposite effects by HLA-DQA1*01 alleles on the HLA-DRB1*15 associated lupus nephritis

HLA-DR2 and namely the allelic variant HLA-DR15 have been associated with lupus nephritis in Caucasoid patients. In this study we investigated the relationships between HLA-class II alleles and lupus nephritis in Italian patients. Two hundreds and forty-four patients, who fulfil the ARA criteria for Systemic Lupus Erythematosus (SLE) were typed for HLA-DRB1*, DQA1*, DQB1* and DPB1* alleles by PCR-SSOP. Seventy-one patients had renal damage, that was assessed by renal biopsy. Glomerulonephritis were classified on the basis of WHO criteria. In our patients, HLA-DQA1*0101 was strongly associated wiyh lupus nephritis (RR=2.82; p<0.005), whereas DRB1* 1501 was only marginally associated (RR=1.8; p=n.s.). On the contrary, HLA-DQA1* showed a significant protective effect (RR=0.30; p<0.005). However, by analysing the distribution of HLA-DRB 1*1501 bearing haplotypes in our SLE patients we found that HLA-DRB1*1501 greatly enhanced the risk to develop lupus nephritis conferred by DQA1*0101 allele, with a RR=65.9, whereas DQA1*0102 suppressed the nephritogenic effect by DRB1*1501 (see Table). Furthemore, the haplotype DRB 1*1501 - DQA1*0101 was strongly associated with diffuse proliferative glomerulonephritis, WHO class IV (RR=36.9; p<0.001). The haplotype DRB1*1501-DQA1*0102 is the most common one among the DR15 haplotypes in the Italian population. Thus, the lack of an overall association between DR15 and lupus nephritis in our patients may be due to the protective effect of DQA1*0102. nephritis +ve (n) nephritis -ve (n) RR p DRB1*1501, DQAI*0101 11 0 65.9 <0.001 DRB1*1501, DQA1*0102 1 21 0.1 <0.001 DRB1*1501, DOA1*0103 3 1 7.6 0.138 © 2001 Blackwell Science Ltd,.