Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with an increased atherosclerotic risk compared to healthy population, partially explained by traditional cardiovascular risk factors. Recent data suggest B-cell activating factor (BAFF) as an important contributor in the pathogenesis of both SLE and atherosclerosis. The aim of the current study is to explore whether genetic variants of the BAFF gene increase SLE susceptibility as well as lupus related atherosclerotic risk

Methods: Five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated in 234 SLE patients and 200 healthy controls (HC) of similar age and sex distribution by PCR-based assays. Allele, genotype and haplotype frequencies in SLE patients and HC were determined by SHEsis and SNPStats software. All patients underwent ultrasound determination of plaque formation in the carotid arteries. Clinical, laboratory and medication data as well as classical risk factors for cardiovascular disease were recorded in all patients. Patients were followed in the Department of Rheumatology, General Hospital of Athens and Rheumatology Unit First Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece between 2013-2016 and fulfilled the American College of Rheumatology (ACR) criteria for the classification of SLE.

Results: The prevalence of the minor A allele and the AA genotype of the rs12583006 BAFF variant was significantly higher in SLE patients compared to HC (OR [95%CI]: 1.51 [1.12-2.04], p=0.007 and OR [95%CI]: 2.62 [1.04-6.61], p=0.03 in recessive model, respectively). Haplotypes TACAT and TTTAT also conferred a heightened risk for lupus susceptibility. Moreover, the AA genotype of the rs12583006 BAFF variant was significantly higher in SLE patients with evidence of atherosclerotic plaque formation compared to those without plaque after adjustment for age and sex (OR[95%CI]: 5.4 [1.5-19.7], p=0.007 in the recessive model). No other significant associations were detected

Conclusion: BAFF genetic variants increase susceptibility to lupus and lupus related atherosclerosis. These data imply B-cell related factors as potential contributors in the pronounced cardiovascular risk among lupus patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-activating-factor-genetic-variants-in-systemic-lupus-erythematosus-and-lupus-related-atherosclerosis/