title: Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis.
abstract: OBJECTIVE
  To determine serum levels of soluble cytotoxic T-lymphocyte associated molecule-4 (sCTLA-4) and clinical association in patients with systemic sclerosis (SSc).
  
  
  METHODS
  Serum sCTLA-4 levels from 32 patients with diffuse cutaneous SSc (dSSc) and 27 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay (ELISA). For a longitudinal study, 211 sera from 30 SSc patients were analysed (follow-up 2.1-7.0 yr).
  
  
  RESULTS
  Serum sCTLA-4 levels were elevated in dSSc patients compared with normal controls (n = 41), lSSc patients and patients with active systemic lupus erythematosus (SLE) (n = 23). By contrast, sCTLA-4 levels in patients with lSSc or SLE were normal. SSc patients with elevated sCTLA-4 levels had a shorter disease duration and more frequent presence of digital pitting scars, contracture of phalanges, diffuse pigmentation, pulmonary fibrosis and decreased percentage vital capacity (%VC) than those with normal sCTLA-4 levels. sCTLA-4 levels correlated positively with the extent of skin fibrosis, serum IgG levels and anti-topoisomerase I antibody levels. In a longitudinal study, sCTLA-4 levels decreased on a parallel with improvement of skin sclerosis in five dSSc patients. Skin sclerosis did not improve in two of six dSSc patients with high sCTLA-4 levels throughout the follow-up, while the remaining four patients showed improvement of skin sclerosis.
  
  
  CONCLUSIONS
  These results suggest that sCTLA-4 correlates with disease severity and activity of SSc and that sCTLA-4 plays a role in immunological abnormalities of SSc, since sCTLA-4 may augment humoral immune responses as well as T-cell responses by interfering with B7-CTLA-4 interactions that induce negative signals in T and B cells.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. s-sato@med.kanazawa-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Komura
authors.forename: K
authors.initials: K
authors.lastname: Yanaba
authors.forename: I
authors.initials: I
authors.lastname: Hayakawa
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: K
authors.initials: K
authors.lastname: Takehara
mesh_terms: D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis; D060908:CTLA-4 Antigen; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000276:immunology; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D045743:Scleroderma, Diffuse / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D012598:Sclerosis / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D012995:Solubility; D013256:Steroids / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007166:Immunosuppressive Agents; D013256:Steroids