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Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations

INTRODUCTION: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-hi...

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Autores principales: Abdulahad, Deena A, Westra, Johanna, Bijzet, Johannes, Dolff, Sebastian, van Dijk, Marcory C, Limburg, Pieter C, Kallenberg, Cees GM, Bijl, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580580/
https://www.ncbi.nlm.nih.gov/pubmed/22892043
http://dx.doi.org/10.1186/ar4015
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author Abdulahad, Deena A
Westra, Johanna
Bijzet, Johannes
Dolff, Sebastian
van Dijk, Marcory C
Limburg, Pieter C
Kallenberg, Cees GM
Bijl, Marc
author_facet Abdulahad, Deena A
Westra, Johanna
Bijzet, Johannes
Dolff, Sebastian
van Dijk, Marcory C
Limburg, Pieter C
Kallenberg, Cees GM
Bijl, Marc
author_sort Abdulahad, Deena A
collection PubMed
description INTRODUCTION: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity. METHODS: The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies. RESULTS: Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4. CONCLUSION: Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation.
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spelling pubmed-35805802013-02-26 Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations Abdulahad, Deena A Westra, Johanna Bijzet, Johannes Dolff, Sebastian van Dijk, Marcory C Limburg, Pieter C Kallenberg, Cees GM Bijl, Marc Arthritis Res Ther Research Article INTRODUCTION: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity. METHODS: The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies. RESULTS: Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4. CONCLUSION: Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation. BioMed Central 2012 2012-08-14 /pmc/articles/PMC3580580/ /pubmed/22892043 http://dx.doi.org/10.1186/ar4015 Text en Copyright ©2012 Abdulahad 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
Abdulahad, Deena A
Westra, Johanna
Bijzet, Johannes
Dolff, Sebastian
van Dijk, Marcory C
Limburg, Pieter C
Kallenberg, Cees GM
Bijl, Marc
Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
title Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
title_full Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
title_fullStr Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
title_full_unstemmed Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
title_short Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
title_sort urine levels of hmgb1 in systemic lupus erythematosus patients with and without renal manifestations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580580/
https://www.ncbi.nlm.nih.gov/pubmed/22892043
http://dx.doi.org/10.1186/ar4015
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