English abstract
Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and systemic inflammation leading to tissue injury. Multiple factors contribute to SLE development, and genetic predisposition is a major factor contributing to SLE susceptibility. Human leukocyte antigen (HLA) genes have received considerable attention among the candidate genes that have been associated with SLĘ worldwide.
Aims: The aim of this study was to investigate if there is any significant relationship between HLA-DRB and HLA-DQB genes and the occurrence of SLE in the Omani population by examining the association between these HLA loci and the risk of developing SLE, the occurrence of renal disorder and presence of anti-double stranded (dsDNA) and anti-Smith (Sm) antibodies in SLE patients.
Methods: This study included 100 controls and 99 SLE patients who attended the Rheumatology Clinic at Sultan Qaboos University Hospital (SQUH) in 2015-2016 and who fulfilled at least four of Systemic Lupus Collaborating Clinics (SLICC) classification criteria. Four milliliters of blood samples were collected from each subject, and genomic DNA was extracted from the blood samples by using QIAamp DNA Blood Midi kits (spin protocol). Then, extracted DNA was genotyped using the low resolution Olerup sequence specific primers (SSP) typing kits and a software program, Score, was used to identify the HLA-DRB and -DQB alleles. The SLE patients' clinical and immunological data were retrieved from the SQUH; Health Information System (HIS).
Results: The distribution frequencies of all the HLA-DRB and -DQB alleles examined were comparable between the SLE patients and control group, and DRB 1*16, DRB1*03, DRB3, DRB5, DQB1*02 and DQB1*05 were the most common alleles detected among the SLE patients and the controls. The association analysis revealed that none of these alleles showed a significant association with SLE among Omani patients. However, DQB1*04 was associated with the presence of renal disorder (p=0.021). Moreover, homozygous DRB1*16,16 and DRB5,5 were significantly associated with the presence of anti-dsDNA antibody (p=0.035 and p=0.018, respectively), and DRB4 was associated with the absence of anti-Sm antibody (p=0.011).
Conclusion: The findings from this study highlight the importance of HLA-DRB and -DQB alleles in antigen presentation to CD4* T cells, suggesting that the allelic variations alter the immune responses that affect autoantibody production and renal damage. The new insight gained from this study may be beneficial for developing patient management approaches that are appropriate for Omani patients with SLE.
