Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis.
Inducible costimulator (ICOS) is crucial for T cell proliferation, production of various cytokines, and T cell-dependent B-cell responses. To determine the serum soluble ICOS (sICOS) level and its association with clinical parameters in patients with systemic sclerosis (SSc), serum sICOS level was examined by enzyme-linked immunosorbent assay in 38 patients with SSc and 24 healthy individuals. The expression of ICOS and ICOS ligand in skin was examined immunohistochemically. There was no significant difference in serum sICOS level between patients with SSc and healthy individuals. Patients with diffuse cutaneous SSc had higher levels of sICOS than those with limited cutaneous SSc (P < 0.05) or healthy individuals (P < 0.05). Serum sICOS level correlated positively with the severity of skin sclerosis. Patients with SSc and elevated sICOS level more often had interstitial lung disease and decreased vital capacity than those with normal sICOS level. The serum sICOS level was significantly greater in patients with early phase SSc than those with late phase SSc. ICOS and ICOS ligand immunostaining were observed on infiltrating dermal mononuclear cells in lesional skin tissue. These results suggest that the serum level of sICOS is increased in patients with diffuse cutaneous SSc and correlates with the severity and activity of skin sclerosis and interstitial lung disease. ICOS may contribute to the development of SSc. In addition, measurement of serum sICOS level in patients with early SSc may offer an important means for further evaluation of SSc disease severity.
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. yanabak-der@h.u-tokyo.ac.jp.
Koichi
K
Yanaba
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yoshihide
Y
Asano
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Shinji
S
Noda
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Kaname
K
Akamata
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Naohiko
N
Aozasa
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Takashi
T
Taniguchi
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Takehiro
T
Takahashi
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yohei
Y
Ichimura
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Tetsuo
T
Toyama
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Hayakazu
H
Sumida
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yoshihiro
Y
Kuwano
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yayoi
Y
Tada
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Makoto
M
Sugaya
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Takafumi
T
Kadono
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Shinichi
S
Sato
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000032:analysis; D060889:Inducible T-Cell Co-Stimulator Protein / Q000097:blood*; D008168:Lung / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D045743:Scleroderma, Diffuse / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation; D014797:Vital Capacity
D015415:Biomarkers; C556692:ICOS protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein