title: Serological assessment of type I collagen burden in scleroderma spectrum disorders: a systematic review.
abstract: BACKGROUND
  The aim of the study was to evaluate the validity of collagen type I metabolites as markers of disease activity in scleroderma (SSc), through a systematic review of the literature and by validating the results by measuring collagen type I metabolites in well characterized patients with scleroderma spectrum disorders and in Raynaud's phenomenon.
  
  
  METHODS
  A systematic review was performed of studies of collagen type I metabolites in scleroderma spectrum disorders published from 1980 to 2003. The collected results from the literature were compared with our own measurements of collagen type I metabolites (PINP and ICTP) in a small number of well characterized patients within the scleroderma spectrum and in patients with primary and "autoimmune" Raynaud's phenomenon. Peptide concentrations from all sources, including the present study, were compared. Reported correlations between peptide concentrations and clinical variables were also analysed.
  
  
  RESULTS
  Of 19 papers identified by an extensive Medline search, 12 were eligible for systematic analysis. There was a considerable heterogeneity in the results with a wide range of metabolite concentrations. Values from disease groups and healthy controls overlapped. These findings were confirmed by our study where, similarly, there was a large range of values in all groups, but particularly in the diffuse SSc subset. When the correlation between peptide levels and clinical variables was assessed, large discordance between the studies was observed.
  
  
  CONCLUSIONS
  We have not found sufficient evidence to support the use of serum markers of collagen turnover in the assessment of scleroderma activity and severity, in view of their low specificity and the heterogeneity of the results of various studies. Lack of standardized routine evaluation of SSc patients in clinical studies might have accounted for the variability of the findings. However, due to the small sizes of most published studies, demonstration of no effect should come from large-scale randomised trials. Longitudinal serial analysis of these molecules in individual patients may play a future role in the evaluation of the response to fibroblast-targeting therapeutic strategies in scleroderma patients.
authors.affiliation: Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Dziadzio
authors.forename: R E
authors.initials: RE
authors.lastname: Smith
authors.forename: D J
authors.initials: DJ
authors.lastname: Abraham
authors.forename: R J
authors.initials: RJ
authors.lastname: Stratton
authors.forename: A
authors.initials: A
authors.lastname: Gabrielli
authors.forename: C M
authors.initials: CM
authors.lastname: Black
authors.forename: C P
authors.initials: CP
authors.lastname: Denton
mesh_terms: D015415:Biomarkers / Q000032:analysis; D024042:Collagen Type I / Q000097:blood*; D006801:Humans; D011928:Raynaud Disease / Q000097:blood / Q000175:diagnosis; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis*; D012698:Serologic Tests
chemical_list: D015415:Biomarkers; D024042:Collagen Type I