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Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study

INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has be...

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Autores principales: Schwartz, Noa, Rubinstein, Tamar, Burkly, Linda C, Collins, Christopher E, Blanco, Irene, Su, Lihe, Hojaili, Bernard, Mackay, Meggan, Aranow, Cynthia, Stohl, William, Rovin, Brad H, Michaelson, Jennifer S, Putterman, Chaim
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787265/
https://www.ncbi.nlm.nih.gov/pubmed/19785730
http://dx.doi.org/10.1186/ar2816
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author Schwartz, Noa
Rubinstein, Tamar
Burkly, Linda C
Collins, Christopher E
Blanco, Irene
Su, Lihe
Hojaili, Bernard
Mackay, Meggan
Aranow, Cynthia
Stohl, William
Rovin, Brad H
Michaelson, Jennifer S
Putterman, Chaim
author_facet Schwartz, Noa
Rubinstein, Tamar
Burkly, Linda C
Collins, Christopher E
Blanco, Irene
Su, Lihe
Hojaili, Bernard
Mackay, Meggan
Aranow, Cynthia
Stohl, William
Rovin, Brad H
Michaelson, Jennifer S
Putterman, Chaim
author_sort Schwartz, Noa
collection PubMed
description INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity. METHODS: Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4. RESULTS: uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity. CONCLUSIONS: High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN.
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spelling pubmed-27872652009-12-02 Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study Schwartz, Noa Rubinstein, Tamar Burkly, Linda C Collins, Christopher E Blanco, Irene Su, Lihe Hojaili, Bernard Mackay, Meggan Aranow, Cynthia Stohl, William Rovin, Brad H Michaelson, Jennifer S Putterman, Chaim Arthritis Res Ther Research article INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity. METHODS: Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4. RESULTS: uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity. CONCLUSIONS: High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN. BioMed Central 2009 2009-09-28 /pmc/articles/PMC2787265/ /pubmed/19785730 http://dx.doi.org/10.1186/ar2816 Text en Copyright ©2009 Schwartz et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
Schwartz, Noa
Rubinstein, Tamar
Burkly, Linda C
Collins, Christopher E
Blanco, Irene
Su, Lihe
Hojaili, Bernard
Mackay, Meggan
Aranow, Cynthia
Stohl, William
Rovin, Brad H
Michaelson, Jennifer S
Putterman, Chaim
Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
title Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
title_full Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
title_fullStr Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
title_full_unstemmed Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
title_short Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
title_sort urinary tweak as a biomarker of lupus nephritis: a multicenter cohort study
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787265/
https://www.ncbi.nlm.nih.gov/pubmed/19785730
http://dx.doi.org/10.1186/ar2816
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