Subclinical atherosclerosis profiles in rheumatoid arthritis and primary Sjögren’s syndrome: the impact of BAFF genetic variations

Abstract

Objectives RA and primary SS carry increased atherosclerotic risk, while B-cell activating factor holds a vital role in disease pathogenesis and atherosclerosis. We aimed to compare subclinical atherosclerosis profiles between the two clinical entities and define whether BAFF genetic variants alter atherosclerotic risk. Methods DNA from 166 RA, 148 primary SS patients and 200 healthy controls of similar age and sex distribution was subjected to PCR-based assay for the detection of five single nucleotide polymorphisms of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and rs9514827). Genotype and haplotype frequencies were determined by SNPStats software and statistical analysis was performed by SPSS and Graphpad Software. Subclinical atherosclerosis was defined by the presence of carotid/femoral plaque formation and arterial wall thickening. Results Atherosclerotic plaque formation was more frequently detected in the RA vs primary SS group (80.7% vs 62.2%, P-value <0.001), along with higher rates of family CVD history, current steroid dose and serum inflammatory markers. The TT genotype of the rs1224141 variant was more prevalent in RA but not primary SS patients with plaque and arterial wall thickening vs their counterparts without. Regarding the rs1014569 variant, among RA patients the TT genotype increased the risk for plaque formation while in primary SS patients the AT genotype conferred increased risk. Haplotype GTTTT was protective in the RA cohort, while TATTT and TTCTT haplotypes increased susceptibility for arterial wall thickening in the primary SS cohort. Conclusions Increased inflammatory burden, higher steroid doses and distinct BAFF gene variations imply chronic inflammation and B-cell hyperactivity as key contributors for the augmented atherosclerotic risk among autoimmune patients.

Associations between TNFSF13B polymorphisms and primary Sjögren's syndrome susceptibility in primary Sjögren's syndrome patients: A meta‐analysis

“…They also demonstrated that genotype TT of rs1041569 was a risk factor for pSS, altering susceptibility to pSS, and that haplotype TTAC also increased susceptibility to pSS. These authors also reported that haplotypes TATTT and TTCTT were only detected in pSS patients with thickened arterial walls 2 . Santillan‐Lopez et al, demonstrated that the expression of TNFSF13B mRNA was increased by 5.04‐fold in pSS patients compared to that in HCs.…”

“…These authors also reported that haplotypes TATTT and TTCTT were only detected in pSS patients with thickened arterial walls. 2 Santillan-Lopez et al, demonstrated that the expression of TNFSF13B mRNA was increased by 5.04-fold in pSS patients compared to that in HCs. They also investigated the relationship between soluble BAFF and TNFSF13B expression and found that elevated TNFSF13B expression levels were consistent with soluble BAFF protein levels.…”

“…Specifically, the TTTAC haplotype was discovered to enhance pSS susceptibility. 2 Another study showed that TNFSF13B mRNA expression was elevated by 2.43-fold and 5.04-fold in patients with RA and pSS compared with healthy controls (HCs), respectively. 3 The findings of a third study suggested that the CTAT haplotype increases disease susceptibility for Ro/La-positive pSS, but is not linked with high serum BAFF (s-BAFF) levels.…”

“…One study showed that the same genotype influences pSS vulnerability in both the codominant and recessive models. Specifically, the TTTAC haplotype was discovered to enhance pSS susceptibility 2 . Another study showed that TNFSF13B mRNA expression was elevated by 2.43‐fold and 5.04‐fold in patients with RA and pSS compared with healthy controls (HCs), respectively 3 .…”

“…TNFSF13B/BAFF is a cytokine that belongs to the TNF ligand family. BAFF aids B‐cell proliferation, maturation, differentiation, and immunoglobulin synthesis 2 . Various single‐nucleotide polymorphisms (SNPs) in TNFSF13B have been linked to vulnerability to various autoimmune diseases 8 …”