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Journal of Clinical Immunology

, Volume 29, Issue 2, pp 180–189 | Cite as

Clinical Significance of Serum HMGB-1 and sRAGE Levels in Systemic Sclerosis: Association with Disease Severity

  • Ayumi Yoshizaki
  • Kazuhiro Komura
  • Yohei Iwata
  • Fumihide Ogawa
  • Toshihide Hara
  • Eiji Muroi
  • Motoi Takenaka
  • Kazuhiro Shimizu
  • Minoru Hasegawa
  • Manabu Fujimoto
  • Shinichi SatoEmail author
Article

Abstract

Introduction

The high mobility group box 1 protein (HMGB-1)/advanced glycation end products (RAGE) system is recently shown to play an important part in immune/inflammatory disorders. However, the association of this system in systemic sclerosis (SSc) remains unknown.

Materials and Methods

To determine clinical association of serum levels of HMGB-1 and soluble RAGE (sRAGE) in patients with SSc, sera from 70 patients with SSc and 25 healthy controls were examined by enzyme-linked immunosorbent assay. Sera from tight-skin mice and bleomycin-induced scleroderma mice, animal models for SSc, were also examined. Skin HMGB-1 and RAGE expression was assessed by immunohistochemistry.

Results and Discussion

Serum HMGB-1 and sRAGE levels in SSc were higher than those in controls. Similarly, HMGB-1 and sRAGE levels in animal SSc models were higher than those in control mice. SSc patients with elevated HMGB-1 and sRAGE levels had more frequent involvement of several organs and immunological abnormalities compared to those with normal levels. Furthermore, HMGB-1 and sRAGE levels correlated positively with modified Rodnan total skin thickness score and negatively with pulmonary function test.

Conclusions

HMGB-1 and sRAGE expression in the sclerotic skin was more intense than normal skin. These results suggest that elevated serum HMGB-1 and sRAGE levels are associated with the disease severity and immunological abnormalities in SSc.

Keywords

HMGB-1 RAGE autoimmune disease systemic sclerosis toll-like receptor 

Notes

Acknowledgment

We thank Ms. Y. Yamada, M. Yozaki, A. Usui, and K. Shimoda for technical assistance. This work was supported by a grant of Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan (to S. Sato).

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ayumi Yoshizaki
    • 1
  • Kazuhiro Komura
    • 1
  • Yohei Iwata
    • 1
  • Fumihide Ogawa
    • 1
  • Toshihide Hara
    • 1
  • Eiji Muroi
    • 1
  • Motoi Takenaka
    • 1
  • Kazuhiro Shimizu
    • 1
  • Minoru Hasegawa
    • 2
  • Manabu Fujimoto
    • 2
  • Shinichi Sato
    • 1
    Email author
  1. 1.Department of DermatologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of DermatologyKanazawa University Graduate School of Medical ScienceKanazawaJapan

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