Clinical significance of serum HMGB-1 and sRAGE levels in systemic sclerosis: association with disease severity.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Yoshizaki
Ayumi
A
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
Komura
Kazuhiro
K
Iwata
Yohei
Y
Ogawa
Fumihide
F
Hara
Toshihide
T
Muroi
Eiji
E
Takenaka
Motoi
M
Shimizu
Kazuhiro
K
Hasegawa
Minoru
M
Fujimoto
Manabu
M
Sato
Shinichi
S
D000328:Adult; D000818:Animals; D005260:Female; D005355:Fibrosis; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000473:pathology*; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic