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

• HLA genes are the most relevant genetic component for SLE disease risk and autoantibodies formation. • DRB1*03 allele was significantly associated with anti-SSA and anti-SSB antibodies production. • DRB1*16 genotypes either homozygote or heterozygote were positively associated with ANA and anti-Sm. • Dominant role of DRB1 over DQB1 alleles was observed for disease predisposition. 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. 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. We found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, P C =0.05 and P = 0.002, P C =0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, P C =0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91, P = 0.01, P C =0.08), DRB1*16~DQB1*05 (OR3.65, P = 0.004,P C =0.06) and DRB1*01~DQB1*05 (OR0.36, P = 0.04, P C =0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (P C =0.02), anti-SSB/La (P C =0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (P C =0.04), DRB1*16 with anti-Sm (P C =0.02), DRB1*04 with anti-β2gpI (P C =3 * 10−5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (P C =0.02) and anti-β2gpI (P C =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. 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. [ABSTRACT FROM AUTHOR]