title: Aberrant expression of membrane cofactor protein and decay-accelerating factor in the endothelium of patients with systemic sclerosis. A possible mechanism of vascular damage.
abstract: BACKGROUND
  One of the main features of systemic sclerosis (SSc) is vascular damage, the mechanism of which is not understood. The aim of this study was to investigate if complement (C) regulatory molecules, membrane cofactor protein (MCP), decay-accelerating factor (DAF), and CD59, which normally protect endothelial cells from damage by autologous C, are absent or down-regulated in vascular endothelium of patients with SSc. A deficiency or persistent down-regulation of the above molecules is likely to render vascular endothelium of these patients susceptible to damage by physiologically or pathologically activated C. From this point of view, expression of MCP, DAF, and CD59 was tested on endothelium of skin of normal subjects and patients with diffuse and limited forms of SSc.
  
  
  METHODS
  Punch biopsies of normal skin (N = 11) and lesional and non-lesional skin of patients with diffuse (N = 5) and limited (N = 5) forms of SSc were obtained and serial sections prepared. Immunoperoxidase staining of these sections was carried out using four monoclonal antibodies (MoAbs) directed to different epitopes of DAF, four to different epitopes of MCP, one to CD59 and one to von Willebrand factor. von Willebrand factor served as a marker of endothelial cells. Besides normal skin, lesional skin of systemic lupus erythematosus and several inflammatory and proliferative diseases, described below, served as controls.
  
  
  RESULTS
  The endothelium of normal skin strongly expressed all the three proteins. However, the endothelium of lesional and nonlesional skin of all the 10 patients with diffuse or limited forms of the disease tested, expressed either decreased or undetectable amounts of MCP and DAF. CD59 expression was normal in some patients and lower than normal in others. Aberrant expression of MCP, DAF, or CD59 was not found in other control inflammatory, connective tissue and proliferative diseases studied.
  
  
  CONCLUSIONS
  In view of the common function of MCP and DAF to protect self cells from autologous C, their decrease or virtual absence from the endothelium of patients with SSc strongly suggests that this deficiency may contribute to vascular damage, resulting in intima proliferation and, finally, fibrosis.
authors.affiliation: Department of Dermatology, University of Amsterdam, The Netherlands.
authors.forename: G T
authors.initials: GT
authors.lastname: Venneker
authors.forename: F H
authors.initials: FH
authors.lastname: van den Hoogen
authors.forename: A M
authors.initials: AM
authors.lastname: Boerbooms
authors.forename: J D
authors.initials: JD
authors.lastname: Bos
authors.forename: S S
authors.initials: SS
authors.lastname: Asghar
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis*; D001706:Biopsy; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D012016:Reference Values; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins