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

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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.

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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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Authors and Affiliations

  1. Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Ayumi Yoshizaki, Kazuhiro Komura, Yohei Iwata, Fumihide Ogawa, Toshihide Hara, Eiji Muroi, Motoi Takenaka, Kazuhiro Shimizu & Shinichi Sato

  2. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

    Minoru Hasegawa & Manabu Fujimoto

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  1. Ayumi Yoshizaki
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  2. Kazuhiro Komura
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Correspondence to Shinichi Sato.

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Yoshizaki, A., Komura, K., Iwata, Y. et al. Clinical Significance of Serum HMGB-1 and sRAGE Levels in Systemic Sclerosis: Association with Disease Severity. J Clin Immunol 29, 180–189 (2009). https://doi.org/10.1007/s10875-008-9252-x

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