Relevance of autoantibody profile with HLA-DRB1 and -DQB1 alleles in a group of Iranian systemic lupus erythematosus patients.

BACKGROUND:One of the most relevant genetic components in systemic lupus erythematosus (SLE) is human leukocyte antigen (HLA) gene complex which plays a central role in autoimmune responses. This study aimed to explore the associations of HLA-DRB1/-DQB1 alleles and haplotypes with SLE risk and the appearance of autoantibodies in SLE disease. METHODS:A total of 127 SLE patients and 153 ethnically matched healthy controls were enrolled. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP method and then HLA alleles and haplotypes frequencies were compared between two groups and among the patients in terms of autoantibodies spectrum. RESULTS:We found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, PC=0.05 and P = 0.002, PC=0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, PC=0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91,P = 0.01, PC=0.08), DRB1*16~DQB1*05 (OR3.65,P = 0.004,PC=0.06) and DRB1*01~DQB1*05 (OR0.36,P = 0.04, PC=0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (PC=0.02), anti-SSB/La (PC=0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (PC=0.04), DRB1*16 with anti-Sm (PC=0.02), DRB1*04 with anti-β2gpI (PC=3 * 10-5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (PC=0.02) and anti-β2gpI (PC=0.01) antibodies. Also, negative associations of DRB1*04 with anti-Sm, anti-SSA/Ro, DQB1*03 with anti-Sm and DRB1*11 with anti-Sm and anti-β2gpI were observed. CONCLUSIONS:We identified DRB1*03 and DRB1*16 as risk alleles and DRB1*01 as a potential protective allele for SLE disease. More importantly, we found a close link between genetic susceptibility for SLE and autoantibodies status that was more evident for DRB1*03 allele.