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Open Access Research article

Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis

Agneta Zickert1*, Karin Palmblad2, Birgitta Sundelin3, Sangeeta Chavan4, Kevin J Tracey4, Annette Bruchfeld5 and Iva Gunnarsson1

Author Affiliations

1 Department of Medicine, Unit of Rheumatology, D2:00 Solna, Karolinska University Hospital, Karolinska Institute, S-171 76 Stockholm, Sweden

2 Women's and Children's Health, Astrid Lindgren Children's Hospital, Solna, Karolinska University Hospital, Karolinska Institute, S-171 76 Stockholm, Sweden

3 Department of Pathology and Cytology, Solna, Karolinska University Hospital, Karolinska Institute, S-171 76 Stockholm, Sweden

4 Laboratory of Biomedical Sciences, Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA

5 Department of Renal Medicine, K56 Huddinge, Karolinska University Hospital, Karolinska Institute, S-141 86 Stockholm, Sweden

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Arthritis Research & Therapy 2012, 14:R36  doi:10.1186/ar3747

Published: 20 February 2012

Abstract

Introduction

High mobility group box 1 protein (HMGB1) is a nuclear DNA binding protein acting as a pro-inflammatory mediator following extracellular release. HMGB1 has been increasingly recognized as a pathogenic mediator in several inflammatory diseases. Elevated serum levels of HMGB1 have been detected in autoimmune diseases including Systemic lupus erythematosus (SLE). However, the local expression of HMGB1 in active lupus nephritis (LN) is not known. Here we aimed to study both tissue expression and serum levels of HMGB1 in LN patients with active disease and after induction therapy.

Methods

Thirty-five patients with active LN were included. Renal biopsies were performed at baseline and after standard induction therapy; corticosteroids combined with immunosuppressive drugs. The biopsies were evaluated according to the World Health Organization (WHO) classification and renal disease activity was estimated using the British Isles lupus assessment group (BILAG) index. Serum levels of HMGB1 were analysed by western blot. HMGB1 expression in renal tissue was assessed by immunohistochemistry at baseline and follow-up biopsies in 25 patients.

Results

Baseline biopsies showed WHO class III, IV or V and all patients had high renal disease activity (BILAG A/B). Follow-up biopsies showed WHO I to II (n = 14), III (n = 6), IV (n = 3) or V (n = 12), and 15/35 patients were regarded as renal responders (BILAG C/D).

At baseline HMGB1 was significantly elevated in serum compared to healthy controls (P < 0.0001). In all patients, serum levels decreased only slightly; however, in patients with baseline WHO class IV a significant decrease was observed (P = 0.03). Immunostaining revealed a pronounced extranuclear HMGB1 expression predominantly outlining the glomerular endothelium and in the mesangium. There was no clear difference in HMGB1 expression comparing baseline and follow-up biopsies or any apparent association to histopathological classification or clinical outcome.

Conclusions

Renal tissue expression and serum levels of HMGB1 were increased in LN. The lack of decrease of HMGB1 in serum and tissue after immunosuppressive therapy in the current study may reflect persistent inflammatory activity. This study clearly indicates a role for HMGB1 in LN.