Expression of BAFF, APRIL, and cognate receptor genes in lupus nephritis and potential use as urinary biomarkers

Abstract

Background B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and their receptors BAFF-R, BCMA, and TACI are crucial factors for the survival of B lymphocytes. Recent evidence has also demonstrated the importance of BAFF/APRIL signaling in lupus nephritis (LN). This study evaluated the relationships between LN clinical characteristics and the urinary expression levels of BAFF, APRIL, and cognate receptors to assess their potential value as disease biomarkers. Methods Expression levels of these genes were assessed in urine samples collected from systemic lupus erythematosus (SLE) patients before renal biopsy using reverse transcription real-time PCR. Results Thirty-five patients with LN were included. Most of the patients were female (82.86%) with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 15. BAFF mRNA was detectable in 28.57%, APRIL mRNA in 42.85%, BR3 mRNA in 48.57%, and TACI mRNA in 42.85% of urine samples. On the other hand, urinary (u)BCMA mRNA was not found in any sample. Urinary expression of most biomarkers was detected with greater frequency in class III and IV LN compared to class V LN. The expression level of uBR3 mRNA was correlated with SLEDAI-2K and histological activity index. Conclusion Urinary expression of BAFF/APRIL signaling factors, especially TACI, APRIL, and BR3 mRNAs, may be useful biomarkers for LN.

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family

“…This was in harmony with previous studies. 15,38,47,48 Herber et al 49 concluded that increased IL-21 level induced deposition of glomerular immune complexes, glomerular basement membrane thickening, and proteinuria in lupus-prone mouse model. Gross et al 50 emphasized that the blocking of the receptors of both TNF-SF13 and BlyS can lower proteinuria.…”

Progress in the application of body fluid and tissue level mRNAs-non-coding RNAs for the early diagnosis and prognostic evaluation of systemic lupus erythematosus

“…The regulatory T lymphocyte recognition marker Foxp3 plays an important role in the pathogenesis of SLE. TACI, APRIL, and BR3 mRNA levels are increased in urine samples from SLE patients ( 36 ), and urinary Foxp3 mRNA levels can be used to assess LN severity and perform risk stratification ( 37 ). Similarly, the urinary and serum levels of CCL2, CCL5, and CXCL10 are increased in active LN patients ( 38 ).…”

Diagnostic test accuracy of novel biomarkers for lupus nephritis—An overview of systematic reviews

“…In recent years, a great scientific effort has been exerted in the search for new biomarkers. Several studies suggest possible candidates, such as genes [ 20 – 23 ], antibodies [ 24 – 26 ], cytokines [ 27 , 28 ], chemokines [ 27 ], adhesion molecules [ 29 – 31 ], growth factors [ 32 , 33 ], cell surface molecules [ 34 ], and cell populations [ 35 , 36 ], among others.…”