title: Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis.
abstract: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc.
  
  
  
  The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of selected patients were stained to detect deposited C3b as a marker of local complement activation.
  
  
  
  Biomarkers of activation of all complement pathways were increased in SSc compared with healthy controls and were similar to those in other rheumatic diseases. When patients with SSc were divided into subgroups, a distinct pattern of complement markers was observed in individuals with scleroderma renal crisis (SRC). By functional assay, we confirmed a significant decrease in complement haemolytic activity in SRC vs. non-SRC patients, indicating complement consumption. Further, we detected glomerular deposits of C3b in some patients with SRC.
  
  
  
  The data indicate that complement activation is an important feature of SRC.
authors.affiliation: Department of Translational Medicine, Section of Medical Protein Chemistry, Lund University, Inga Marie Nilssons Street 53, Malmö, S-20502, Sweden.|Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, Gdańsk, 80210, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Okrój
authors.affiliation: Department of Translational Medicine, Section of Clinical Pathology, Lund University, Jan Waldenströms street 59, Malmö, S-20502, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, Skåne University Hospital, Lund, S-22185, Sweden.
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.affiliation: Department of Translational Medicine, Section of Medical Protein Chemistry, Lund University, Inga Marie Nilssons Street 53, Malmö, S-20502, Sweden. anna.blom@med.lu.se.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, Skåne University Hospital, Lund, S-22185, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation / Q000502:physiology*; D003179:Complement C3b / Q000032:analysis*; D015935:Complement C4b; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D003179:Complement C3b; D015935:Complement C4b; C032261:complement C4d
keywords: Biomarkers; Complement; Renal crisis; Scleroderma; Systemic sclerosis