Role of tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible molecule 14 pathway in lupus nephritis

Abstract

Objectives To evaluate urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) levels as well as renal fibroblast growth factor-inducible molecule 14 (Fn14) expression by immunohistochemistry in patients with systemic lupus erythematosus (SLE) to assess the possible role of TWEAK level as an indicator of lupus nephritis (LN) and its relation to disease activity as well as pathological LN classification. Patients and methods Urinary levels of TWEAK using enzyme-linked immunosorbent assay and chemical and immunological markers of SLE were measured in 30 patients with SLE and 15 age-matched and sex-matched apparently healthy controls. Patients with SLE were divided into two subgroups: 15 patients with LN and 15 without LN. Disease activity was assessed using systemic lupus erythematosus disease activity index SLE disease activity index (SLEDAI). Fn14 was examined in renal biopsies from LN group by immunohistochemistry. Results A significantly higher uTWEAK level was found in patients having SLE with LN compared with those without LN and controls (F=149.2, P<0.001). uTWEAK had a highly significant positive correlation with proteinuria (r=0.755, P<0.001) and a significant positive correlation with tSLEDAI and rSLEDAI (r=0.217, P<0.037 and r=0.476, P<0.024, respectively). uTWEAK had a significant negative correlation with anti-dsDNA titer, C3, and C4 (r=−0.579, P<0.008; r=−0.456, P<0.011; and r=−0.552, P<0.002, respectively). Fn14 expression was detected in mesangial and tubular cells, mainly proximal tubular cells, in patients with LN. Conclusion uTWEAK is a specific and sensitive biomarker for detection of active LN.

Keywords

• biomarker
• lupus nephritis
• systemic lupus erythematosus
• tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible molecule 14