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Urinary levels of high mobility group box-1 are associated with disease activity in antineutrophil cytoplasmic autoantibody-associated vasculitis.

Ma TT, Wang H, Wang C, Chang DY, Zhao MH, Chen M - PLoS ONE (2015)

Bottom Line: Our previous study demonstrated that the circulating levels of HMGB1 correlated with disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).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).Urinary levels of HMGB1 may be associated with the disease activity in AAV patients.

View Article: PubMed Central - PubMed

Affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

ABSTRACT

Background: High 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.

Methods: 50 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.

Results: Urinary 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).

Conclusion: Urinary levels of HMGB1 may be associated with the disease activity in AAV patients.

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Expression of HMGB1 in renal tissue of active AAV patients and controls.A and B showed isotype Ig staining in control renal tissue. Biopsy taken from normal renal tissue showed expression of HMGB1 mainly inside nuclei (C, D). Renal tissue of the active AAV patient showed strong cytoplasmic and extracellular staining for HMGB1 in tubuli and glomeruli (E, F).
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pone.0123586.g004: Expression of HMGB1 in renal tissue of active AAV patients and controls.A and B showed isotype Ig staining in control renal tissue. Biopsy taken from normal renal tissue showed expression of HMGB1 mainly inside nuclei (C, D). Renal tissue of the active AAV patient showed strong cytoplasmic and extracellular staining for HMGB1 in tubuli and glomeruli (E, F).

Mentions: In normal renal tissues, HMGB1 was mainly present in the nuclei. However, in biopsy sections from patients with AAV in active stage, HMGB1 was mainly expressed in the cytoplasm and the extracellular space (Fig 4). 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). No significant correlation was found between the percentage of HMGB1 negative nuclei in the kidney and histological or clinical findings.


Urinary levels of high mobility group box-1 are associated with disease activity in antineutrophil cytoplasmic autoantibody-associated vasculitis.

Ma TT, Wang H, Wang C, Chang DY, Zhao MH, Chen M - PLoS ONE (2015)

Expression of HMGB1 in renal tissue of active AAV patients and controls.A and B showed isotype Ig staining in control renal tissue. Biopsy taken from normal renal tissue showed expression of HMGB1 mainly inside nuclei (C, D). Renal tissue of the active AAV patient showed strong cytoplasmic and extracellular staining for HMGB1 in tubuli and glomeruli (E, F).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401773&req=5

pone.0123586.g004: Expression of HMGB1 in renal tissue of active AAV patients and controls.A and B showed isotype Ig staining in control renal tissue. Biopsy taken from normal renal tissue showed expression of HMGB1 mainly inside nuclei (C, D). Renal tissue of the active AAV patient showed strong cytoplasmic and extracellular staining for HMGB1 in tubuli and glomeruli (E, F).
Mentions: In normal renal tissues, HMGB1 was mainly present in the nuclei. However, in biopsy sections from patients with AAV in active stage, HMGB1 was mainly expressed in the cytoplasm and the extracellular space (Fig 4). 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). No significant correlation was found between the percentage of HMGB1 negative nuclei in the kidney and histological or clinical findings.

Bottom Line: Our previous study demonstrated that the circulating levels of HMGB1 correlated with disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).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).Urinary levels of HMGB1 may be associated with the disease activity in AAV patients.

View Article: PubMed Central - PubMed

Affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

ABSTRACT

Background: High 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.

Methods: 50 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.

Results: Urinary 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).

Conclusion: Urinary levels of HMGB1 may be associated with the disease activity in AAV patients.

Show MeSH
Related in: MedlinePlus