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Molecular Medicine

, Volume 17, Issue 1–2, pp 29–35 | Cite as

High-Mobility Group Box-1 Protein (HMGB1) Is Increased in Antineutrophilic Cytoplasmatic Antibody (ANCA)-Associated Vasculitis with Renal Manifestations

  • Annette Bruchfeld
  • Marten Wendt
  • Johan Bratt
  • Abdul R. Qureshi
  • Sangeeta Chavan
  • Kevin J. Tracey
  • Karin Palmblad
  • Iva Gunnarsson
Research Article

Abstract

High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is increasingly recognized as an important proinflammatory mediator actively secreted from monocytes and macrophages and passively released from necrotic cells. In antineutrophilic cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), the kidneys are commonly affected vital organs, characterized by focal necrotizing and/or crescentic pauci-immune glomerulonephritis. The aim of the study was to determine whether HMGB1 serum levels are elevated in AAV with renal manifestations. A total of 30 AAV patients (16 female and 14 male; median age 59 years, range 17–82) with Wegener granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome with available renal biopsies and serum samples were included. In seven cases, serum was also obtained at rebiopsy in remission. HMGB1 was analyzed with Western blot. Birmingham Vasculitis Activity Score (BVAS, version 2003), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), urinanalysis, creatinine, estimated glomerular filtration rate, sex and age were included in the analysis. Twenty-five episodes of biopsy-proven active disease with BVAS 17.9 ± 4.6 and 13 cases with inactive biopsies and BVAS 2.3 ± 3.7 (P = 0.0001) were identified. CRP ESR, hematuria and proteinuria were significantly higher in active cases. HMGB1 was significantly elevated (P= 0.01) comparing active with inactive cases (120 ± 48 versus 78 ± 46 ng/mL) and significantly lower in the seven control patients (P = 0.03) at rebiopsy in remission. HMGB1 remained higher in inactive cases compared with historic healthy controls (10.9 ± 10.5 ng/mL). HMGB1 levels did not differ significantly between AAV subgroups. CRP and ESR did not correlate with HMGB1. HMGB1 is significantly increased in AAV with renal involvement. Residual HMGB1 elevation in remission could possibly reflect low-grade inflammatory activity or tissue damage. Future studies may further reveal whether HMGB1 is useful as a marker of disease activity and a predictor of outcome in AAV.

Notes

Acknowledgments

We thank Westman Research Fund, Karolinska Institutet Funds, The Swedish League Against Rheumatism, King Gustav V:S Memorial Fund, the Swedish Research Council, The Swedish Society of Medicine and the Fund for Renal Research.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Annette Bruchfeld
    • 1
  • Marten Wendt
    • 1
  • Johan Bratt
    • 2
  • Abdul R. Qureshi
    • 1
  • Sangeeta Chavan
    • 3
  • Kevin J. Tracey
    • 3
  • Karin Palmblad
    • 4
  • Iva Gunnarsson
    • 2
  1. 1.Department of Renal MedicineCLINTEC, Karolinska InstituteStockholmSweden
  2. 2.Unit of Rheumatology, Department of Medicine, Karolinska Institute, K 56Karolinska University Hospital at HuddingeStockholmSweden
  3. 3.Laboratory of Biomedical Sciences, Feinstein Institute for Medical ResearchNorth Shore-LIJ Health SystemManhassetUSA
  4. 4.Women’s and Children’s Health, Astrid Lindgren Children’s HospitalKarolinska University Hospital, Karolinska InstituteStockholmSweden

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