Abstract

ObjectivesTo 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 methodsUrinary 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.ResultsA 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.ConclusionuTWEAK is a specific and sensitive biomarker for detection of active LN.

Highlights

  • Systemic lupus erythematosus (SLE) is arguably the most serologically and clinically diverse multisystem autoimmune disease characterized by autoantibody production, immune complex formation, and immunologically mediated tissue injury [1].Renal involvement is the most common and serious manifestation of SLE

  • Several studies have found that a disorder of the regulation of apoptosis is an important factor in SLE progress, such as TWEAK, and might play an important role in the pathogenesis of lupus nephritis (LN) [10]

  • We found that uTWEAK levels were significantly positively correlated with tSLEDAI and rSLEDAI (P

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Summary

Introduction

Systemic lupus erythematosus (SLE) is arguably the most serologically and clinically diverse multisystem autoimmune disease characterized by autoantibody production, immune complex formation, and immunologically mediated tissue injury [1].Renal involvement is the most common and serious manifestation of SLE. The cytokine tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), known as TNF ligand superfamily member 12, is a pleiotropic and multifunctional cytokine member of the TNF superfamily that regulates inflammatory pathways by inducing multiple cellular responses depending on the cell type and its microenvironment. It binds to its receptor, fibroblast growth factor-inducible molecule 14 (Fn14), stimulating a wide array of physiological processes, such as cellular proliferation, migration, survival, differentiation, and induction of apoptosis [3].

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