title: Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis.
abstract: BACKGROUND
  A disintegrin and metalloprotease (ADAM) 12 is one of the metalloproteinase-type ADAMs and possesses extracellular metalloprotease and cell-binding functions. ADAM12 is expressed in two alternative forms, such as a membrane-anchored form (ADAM12-L) and a short secreted form (ADAM12-S).
  
  
  OBJECTIVE
  To investigate the clinical significance of serum ADAM12-S levels in systemic sclerosis (SSc).
  
  
  METHODS
  Serum ADAM12-S levels were determined by a specific enzyme-linked immunosorbent assay in 61 SSc patients and 18 healthy controls.
  
  
  RESULTS
  Serum ADAM12-S levels were significantly increased in diffuse cutaneous SSc (dcSSc) patients than in healthy controls (0.417 ± 0.389 vs. 0.226 ± 0.065 ng/mL; P < 0.05), while being comparable between limited cutaneous SSc (0.282 ± 0.258 ng/mL) and healthy controls. Serum ADAM12-S levels significantly elevated in dcSSc patients with disease duration of ≤ 6 years (0.537 ± 0.449 ng/mL, P < 0.05), but not in dcSSc with disease duration of >6 years (0.225 ± 0.049 ng/mL), compared to healthy controls. Furthermore, in dcSSc patients with disease duration of ≤ 6 years, serum ADAM12-S levels correlated positively with modified Rodnan total skin thickness score, ground glass score, and serum C-reactive protein values, while showed inverse correlation with fibrosis score.
  
  
  CONCLUSIONS
  Elevated serum ADAM12-S levels are associated with elevated serum inflammatory marker, severity of skin fibrosis, and activity of interstitial lung disease in dcSSc, suggesting the possible contribution of ADAM12-S to the pathological events in this disorder.
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Asano
authors.forename: K
authors.initials: K
authors.lastname: Akamata
authors.forename: N
authors.initials: N
authors.lastname: Aozasa
authors.forename: S
authors.initials: S
authors.lastname: Noda
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ichimura
authors.forename: T
authors.initials: T
authors.lastname: Toyama
authors.forename: H
authors.initials: H
authors.lastname: Sumida
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwano
authors.forename: K
authors.initials: K
authors.lastname: Yanaba
authors.forename: Y
authors.initials: Y
authors.lastname: Tada
authors.forename: M
authors.initials: M
authors.lastname: Sugaya
authors.forename: T
authors.initials: T
authors.lastname: Kadono
authors.forename: S
authors.initials: S
authors.lastname: Sato
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000072199:ADAM12 Protein; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000209:etiology; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000209:etiology*; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications*; D012867:Skin / Q000473:pathology; D013997:Time Factors
chemical_list: D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human