Are urinary levels of high mobility group box 1 markers of active nephritis in anti-neutrophil cytoplasmic antibody-associated vasculitis?

Souza, Alexandre Wagner Silva de; Abdulahad, Wayel H.; Sosicka, Paulina; Bijzet, J.; Limburg, Pieter C.; Stegeman, Coen A.; Bijl, Marc; Westra, Johanna; Kallenberg, Cornelis

doi:10.1111/cei.12422

Cited by 19 publications

(11 citation statements)

References 35 publications

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“…In the present study, we demonstrated that the urinary levels of HMGB1 in active AAV patients were significantly higher than AAV patients in remission and healthy controls. Moreover, the level of HMGB1 in remission was lower than that in active phase for most patients with sequential urine samples, which was in line with the study by de Souza et al [ 22 ]. Further assessment revealed that the urinary HMGB1 level correlated with ESR, CRP and BVAS, which are commonly used parameters to evaluate the disease activity of AAV.…”

Section: Discussionsupporting

confidence: 91%

Urinary Levels of High Mobility Group Box-1 Are Associated with Disease Activity in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Wang

et al. 2015

PLoS ONE

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BackgroundHigh mobility group box-1 (HMGB1), a kind of pro-inflammatory mediator, is associated with inflammatory conditions and tissue damage. Our previous study demonstrated that the circulating levels of HMGB1 correlated with disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the current study, we aimed to measure urinary levels of HMGB1 in AAV patients, correlated them to clinical activity index and analysed the immunohistochemical HMGB1 staining in kidney specimens.Methods50 patients with AAV in active stage and 56 patients with AAV in remission were recruited. The urinary levels of HMGB1 were determined by enzyme-linked immunosorbent assay. Moreover, renal biopsy specimens from 27 patients with active AAV were randomly collected to evaluate the deposition of HMGB1.ResultsUrinary HMGB1 levels in AAV patients in active stage were significantly higher than those in AAV patients in remission and healthy controls (1.46 [0.56-3.43] versus 0.38 [0.10-1.35] mg/μmolCr, P=0.001; 1.46 [0.56-3.43] versus 0.48 [0.40-0.60] mg/μmolCr, P=0.000, respectively). Further analysis found that urinary levels of HMGB1 correlated with erythrocyte sedimentation rate (r=0.354, p=0.012), C-reactive protein (r=0.289, p=0.042), and Birmingham Vasculitis Activity Score (r=0.350, p=0.013). Renal tissue of active AAV patients showed HMGB1 was mainly expressed in the cytoplasm and the extracellular space. The percentage of HMGB1-negative nuclei in renal tissue of patients with active AAV was significantly higher than that in normal controls (60.6±20.2 % versus 2.7±0.6 %, p<0.01).ConclusionUrinary levels of HMGB1 may be associated with the disease activity in AAV patients.

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Section: Discussionsupporting

confidence: 91%

Urinary Levels of High Mobility Group Box-1 Are Associated with Disease Activity in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Wang

et al. 2015

PLoS ONE

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“…After binding to HMGB1, RAGE mediates multiple intracellular signaling pathways, including NF-κB, JAK/STAT, and MAPK families, and exerts a wide range of physiological and pathological effects [26]. HMGB1 levels have been shown to be higher in 27 children by KD than in healthy controls, as measured by Hoshina [27][28][29]. In order to be consistent with these studies, we collected serum samples from children in different phases of KD.…”

Section: Discussionmentioning

confidence: 87%

Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury

et al. 2020

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Background: Kawasaki disease (KD) is a common, yet unknown etiology disease in Asian countries, which causes acquired heart disease in childhood. It is characterized by an inflammatory acute febrile vasculitis of medium-sized arteries, particularly the coronary arteries. High-mobility group box-1 protein (HMGB1) is a non-histone chromosomalbinding protein present in the nucleus of eukaryotic cells, which contains 215 amino acid residues. Although the cellular signal transduction mechanisms of HMGB1 are currently unclear, the important role of the receptor for advanced glycation end-products (RAGE), the main receptor for HMGB1 has been reported in detail. The purpose of our study was to verify the mechanism and clinical significance of HMGB1-RAGE in coronary artery injury of Kawasaki disease. Methods: 52 blood samples of patients in KD were collected, and the coronary artery Z score was calculated according to the echocardiographic results. The Z score ≥ 2.0 was classified as coronary artery lesions (CAL); otherwise, it was no-coronary artery lesions (NCAL). In addition, the fever group and control group were set. Among them, the fever group were children with fever due to respiratory tract infection at the same time period as KD (heat peak ≥ 38.5 ℃). The normal group were children at a routine physical examination in the outpatient clinic of Nantong University and the physical examination center of the child care insurance, and there were no infectious diseases and heart diseases. The serum levels of HMGB1, RAGE, and NF-κB in each group were detected by ELISA. The animal model of KD was established using the New Zealand young rabbits. We used RT-qPCR/H&E staining/immunohistochemistry/ELISA and western blot to detect the level of HMGB1/RAGE and NF-κB. Results: In this study, we found that the HMGB1/RAGE/NF-κB axis was elevated in the serum of children with KD. In addition, an animal model of KD was subsequently prepared to examine the pathological changes of the coronary arteries. We found that the serum levels of HMGB1/RAGE/NF-κB in rabbits with KD were significantly higher than those of the control group. Moreover, the lumen diameter of the coronary artery was slightly enlarged, and the wall of the tube became thinner and deformed. In addition, the HMGB1/RAGE/NF-κB levels in the coronary artery were higher in the rabbits with KD in the acute phase. Conclusions: On the whole, the findings of this study demonstrate that the expression of HMGB1/RAGE/NF-κB is altered at different stages of KD, suggesting that the HMGB1/RAGE/NF-κB signaling pathway plays an important role in vascular injury in KD. The results of this study may have important implications for the early warning of coronary artery lesions in KD.

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“…Recently, we observed circulating HMGB1 levels are associated with the disease activity of AAV [ 14 ], which was in line with and further extended the earlier related findings [ 38 - 40 ], although it remains controversial in studies by de Souza et al . [ 41 , 42 ]. Whether HMGB1 participated in the pathogenesis of AAV, and then the underlying mechanism was not fully clear yet.…”

Section: Discussionmentioning

confidence: 99%

High mobility group box 1 contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation through receptor for advanced glycation end products (RAGE) and Toll-like receptor 4

Wang¹,

Wang²,

Chang³

et al. 2015

Arthritis Res Ther

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Introduction: High mobility group box-1 (HMGB1), a typical damage-associated molecular pattern (DAMP) protein, is associated with inflammatory conditions and tissue damage. Our recent study found that circulating HMGB1 levels could reflect the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to investigate whether HMGB1 participated in ANCA-induced neutrophil activation, which is one of the most important pathogenic aspects in the development of AAV.

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Are urinary levels of high mobility group box 1 markers of active nephritis in anti-neutrophil cytoplasmic antibody-associated vasculitis?

Abstract: SummaryThe objective of this study is to evaluate urinary high mobility group box 1 (HMGB1) levels as markers for active nephritis in patients with antineutrophil cytoplasmic antibody (

Cited by 19 publications

References 35 publications

Urinary Levels of High Mobility Group Box-1 Are Associated with Disease Activity in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Urinary Levels of High Mobility Group Box-1 Are Associated with Disease Activity in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury

High mobility group box 1 contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation through receptor for advanced glycation end products (RAGE) and Toll-like receptor 4

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