title: The local complement activation on vascular bed of patients with systemic sclerosis: a hypothesis-generating study.
abstract: OBJECTIVE
  The role of complement system in the pathogenesis of systemic sclerosis (SSc) has been debated during the last decade but an evident implication in this disease has never been found. We carried out an explorative study on SSc patients to evaluate the expression of soluble and local C5b-9 complement complex and its relation with a complement regulator, the Membrane Cofactor Protein (MCP, CD46) on skin vascular bed as target distinctive of SSc disease. We also analyzed two polymorphic variants in the complement activation gene cluster involving the MCP region.
  
  
  METHODS
  C5b-9 plasma levels of SSc patients and healthy subjects were analyzed by ELISA assay. Archival skin biopsies of SSc patients and controls were subjected to immunofluorescence analysis to detect C5b-9 and MCP on vascular endothelial cells. The expression of MCP was validated by immunoblot analysis with specific antibody. Polymorphic variants in the MCP gene promoter were tested by a quantitative PCR technique-based allelic discrimination method.
  
  
  RESULTS
  Even though circulating levels of C5b-9 did not differ between SSc and controls, C5b-9 deposition was detected in skin biopsies of SSc patients but not in healthy subjects. MCP was significantly lower in skin vessels of SSc patients than in healthy controls and was associated with the over-expression of two polymorphic variants in the MCP gene promoter, which has been related to more aggressive phenotypes in other immune-mediated diseases.
  
  
  CONCLUSIONS
  Our results firsty document the local complement activation with an abnormal expression of MCP in skin vessels of SSc patients, suggesting that a subset of SSc patients might be exposed to more severe organ complications and clinical evolution due to abnormal local complement activation.
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Cinzia
authors: C
authors: Scambi
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Sara
authors: S
authors: Ugolini
authors: Department of Bacteriology and Immunology, Haartman Institute and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
authors: T Sakari
authors: TS
authors: Jokiranta
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Lucia
authors: L
authors: De Franceschi
authors: Research Support Unit and Biostatistics, Verona University Hospital, Verona, Italy.
authors: Oscar
authors: O
authors: Bortolami
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Valentina
authors: V
authors: La Verde
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Patrizia
authors: P
authors: Guarini
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Paola
authors: P
authors: Caramaschi
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Viviana
authors: V
authors: Ravagnani
authors: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors: Guido
authors: G
authors: Martignoni
authors: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors: Chiara
authors: C
authors: Colato
authors: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors: Serena
authors: S
authors: Pedron
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Fabio
authors: F
authors: Benedetti
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Marco
authors: M
authors: Sorio
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Fabio
authors: F
authors: Poli
authors: Department of Medicine, University of Verona, Verona, Italy.
authors: Domenico
authors: D
authors: Biasi
mesh_terms: D000368:Aged; D003167:Complement Activation / Q000235:genetics*; D015938:Complement Membrane Attack Complex / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012595:Scleroderma, Systemic / Q000097:blood / Q000235:genetics / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000473:pathology
chemical_list: C497857:CD46 protein, human; D015938:Complement Membrane Attack Complex; D051916:Membrane Cofactor Protein