title: Skin involvement in scleroderma--where histological and clinical scores meet.
abstract: OBJECTIVE
  A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS).
  
  
  METHODS
  Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT).
  
  
  RESULTS
  Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies).
  
  
  CONCLUSIONS
  The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.
authors.affiliation: INSERM U697, Paris, France. franck.verrecchia@stlouis.inserm.fr
authors.forename: F
authors.initials: F
authors.lastname: Verrecchia
authors.forename: J
authors.initials: J
authors.lastname: Laboureau
authors.forename: O
authors.initials: O
authors.lastname: Verola
authors.forename: N
authors.initials: N
authors.lastname: Roos
authors.forename: R
authors.initials: R
authors.lastname: Porcher
authors.forename: P
authors.initials: P
authors.lastname: Bruneval
authors.forename: M
authors.initials: M
authors.lastname: Ertault
authors.forename: K
authors.initials: K
authors.lastname: Tiev
authors.forename: L
authors.initials: L
authors.lastname: Michel
authors.forename: A
authors.initials: A
authors.lastname: Mauviel
authors.forename: D
authors.initials: D
authors.lastname: Farge
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D024042:Collagen Type I; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D045743:Scleroderma, Diffuse / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D012720:Severity of Illness Index; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D051785:Smad Proteins / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; C497790:SMAD3 protein, human; D051785:Smad Proteins; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen