Urinary TWEAK and the activity of lupus nephritis
Division of Rheumatology, Forchheimer 701N, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Journal of Autoimmunity
(Impact Factor: 8.41).
12/2006; 27(4):242-50. DOI: 10.1016/j.jaut.2006.12.003
The TNF superfamily cytokine TWEAK induces mesangial cells, podocytes, and endothelial cells to secrete pro-inflammatory chemokines including MCP-1, IP-10 and RANTES, which are crucial in the pathogenesis of lupus nephritis (LN). As TWEAK regulates the secretion of these inflammatory mediators, we studied whether urinary TWEAK (uTWEAK) levels might be predictive and/or diagnostic in LN. In a cross-sectional study of a large, multi-center cohort of systemic lupus erythematosus (SLE) patients, uTWEAK levels were higher in patients with active as compared to never or non-active nephritis (median (IQR): 16.3 (9.9-23.0) versus 5.5 (2.3-16.8) pg/mg creatinine, p=0.001), and levels of uTWEAK correlated with the renal SLE disease activity index (rSLEDAI) score (r=0.405, p<0.001). uTWEAK levels were higher in patients undergoing a flare as compared to patients with chronic stable disease (11.1 (8.1-18.2) and 5.2 (2.3-15.3) pg/mg creatinine, respectively; p=0.036). Moreover, uTWEAK levels were significantly higher in patients undergoing a renal flare, as opposed to a non-renal flare (12.4 (9.1-18.2) and 5.2 (3.0-11.9) pg/mg creatinine, respectively; p=0.029). An accurate, non-invasive method to repeatedly assess kidney disease in lupus would be very helpful in managing these often challenging patients. Our study indicates that urinary TWEAK levels may be useful as a novel biomarker in LN.
Available from: sciencedirect.com
- "From a serological point of view, SLE diagnosis could be improved especially in those cases that are considered borderline for the autoantibody titre or uncertain for their incomplete clinical manifestations, as observed in other diseases. A new multiplex immunoassay is under     investigation for its capacity to detect eight cytokines, in particular IP-10 , IL-8  and TNF-α  that are elevated in SLE patients (Y. Zhizhong, China). "
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ABSTRACT: Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics, from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondiloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral Jak inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology.
Available from: Michel Khrestchatisky
- "In urine, LN patients have been compared with control subjects but data obtained in this latter group was detailed by only one team in 23 healthy volunteers with a reference value for uTWEAK of 5.67 pg/mg of creatinine (interquartile range: 3.10) (5, 6, 19). "
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ABSTRACT: The TWEAK/Fn14 pathway is now well-known for its involvement in the modulation of inflammation in various human autoimmune/chronic inflammatory diseases (AICID) including lupus, rheumatoid arthritis, and multiple sclerosis. A panel of data is now available concerning TWEAK expression in tissues or biological fluids of patients suffering from AICID, suggesting that it could be a promising biological marker in these diseases. Evidences from several teams support the hypothesis that blocking TWEAK/Fn14 pathway is an attractive new therapeutic lead in such diseases and clinical trials with anti-TWEAK-blocking antibodies are in progress. In this mini-review we discuss the potential use of TWEAK quantification in AICD management in routine practice and highlight the challenge of standardizing data collection to better estimate the clinical utility of such a biological parameter.
Available from: Jonay Poveda
- "In human lupus nephritis glomerular Fn14 mRNA expression was increased and was higher in proliferative than in membranous lupus nephropathy (27, 28). Urinary TWEAK has been proposed as a biomarker of lupus nephritis activity (29–32). "
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ABSTRACT: The incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) is increasing. However, there is no effective therapy for AKI and current approaches only slow down, but do not prevent progression of CKD. TWEAK is a TNF superfamily cytokine. A solid base of preclinical data suggests a role of therapies targeting the TWEAK or its receptor Fn14 in AKI and CKD. In particular TWEAK/Fn14 targeting may preserve renal function and decrease cell death, inflammation, proteinuria, and fibrosis in mouse animal models. Furthermore there is clinical evidence for a role of TWEAK in human kidney injury including increased tissue and/or urinary levels of TWEAK and parenchymal renal cell expression of the receptor Fn14. In this regard, clinical trials of TWEAK targeting are ongoing in lupus nephritis. Nuclear factor-kappa B (NF-κB) activation plays a key role in TWEAK-elicited inflammatory responses. Activation of the non-canonical NF-κB pathway is a critical difference between TWEAK and TNF. TWEAK activation of the non-canonical NF-κB pathways promotes inflammatory responses in tubular cells. However, there is an incomplete understanding of the role of non-canonical NF-κB activation in kidney disease and on its contribution to TWEAK actions in vivo.
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