B-cell activating factor and A proliferation-inducing ligand in relation to intima-media thickness as biomarkers of premature atherosclerosis in systemic lupus erythematosus patients

Am J Med Sci. 2022 Nov;364(5):646-654. doi: 10.1016/j.amjms.2022.05.008. Epub 2022 May 14.

Abstract

Background: The aim of this study was to assess the correlation of the serum B-cell activating factor (BAFF), A proliferation-inducing ligand (APRIL) and interleukin (IL)-21 with carotid intima-media thickness (cIMT) to evaluate their efficacy as non-invasive biomarkers for the risk of premature development of atherosclerosis.

Methods: ELISA test was used to quantify serum BAFF, APRIL and IL-21 in 40 patients with systemic lupus erythematosus (SLE) and 20 healthy controls (HCs). The obtained results were correlated with disease duration, anti-double stranded DNA, complement proteins levels, lipid profile, cIMT and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Results: Serum BAFF, APRIL and IL-21 were significantly increased in SLE compared to HCs. Positive correlation was recorded between BAFF (r = 0.51) and APRIL (r = 0.52) with the cIMT. IL-21 correlated positively with SLEDAI (r = 0.33) and negatively with BAFF (r = -0.37) and APRIL (r = -0.44). According to the multiple logistic regression analysis, we found that low-density lipoprotein, serum BAFF and APRIL values were independent factors for cIMT in SLE. To discriminate premature atherosclerosis in patients with SLE, BAFF ≥455 pg/ml yielded 88.9% sensitivity with 100% specificity while APRIL ≥600 pg/ml yielded 95% sensitivity with 100% specificity. IL-21 ≥240 pg/ml yielded 66.7% sensitivity and 100% specificity.

Conclusions: Circulating BAFF and APRIL in patients with SLE were correlated to disease activity and cIMT, suggesting that they could be used as a peripheral blood biomarker for the occurrence of premature atherosclerosis in SLE.

Keywords: APRIL; Atherosclerosis; BAFF; IL-21; SLE.

MeSH terms

  • Atherosclerosis* / blood
  • Atherosclerosis* / etiology
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • B-Cell Activating Factor* / blood
  • B-Cell Activating Factor* / genetics
  • B-Cell Activating Factor* / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Carotid Intima-Media Thickness*
  • Complement System Proteins
  • DNA
  • Humans
  • Interleukin-4
  • Lipids
  • Lipoproteins, LDL
  • Lupus Erythematosus, Systemic* / blood
  • Lupus Erythematosus, Systemic* / complications
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Erythematosus, Systemic* / metabolism

Substances

  • B-Cell Activating Factor
  • Biomarkers
  • Complement System Proteins
  • DNA
  • Interleukin-4
  • Lipids
  • Lipoproteins, LDL
  • TNFSF13 protein, human
  • interleukin-21