title: CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis.
abstract: BACKGROUND
  CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence.
  
  
  METHODS
  Synovial tissue, primary FLS cultures, and three-dimensional FLS micromasses were analyzed. CD55 expression was assessed by quantitative polymerase chain reaction (PCR), in situ hybridization, flow cytometry, and immunohistochemistry. Reticular fibers were visualized by Gomori staining and colocalization of CD55 with extracellular matrix (ECM) proteins by confocal microscopy. Membrane-bound CD55 was released from synovial tissue with phospholipase C. Functional consequences of CD55 expression were studied in the K/BxN serum transfer model of arthritis using mice that in addition to CD55 also lack FcγRIIB (CD32), increasing susceptibility for immune complex-mediated pathology.
  
  
  RESULTS
  Abundant CD55 expression seen in FLS of the intimal lining layer was associated with linearly oriented reticular fibers and was resistant to phospholipase C treatment. Expression of CD55 colocalized with collagen type I and III as well as with complement C3. A comparable distribution of CD55 was established in three-dimensional micromasses after ≥3 weeks of culture together with the ECM. CD55 deficiency did not enhance K/BxN serum-induced arthritis, but further exaggerated disease activity in Fcgr2b (-/-) mice.
  
  
  CONCLUSIONS
  CD55 is produced by FLS and deposited on the local collagen fiber meshwork, where it protects the synovial tissue against immune complex-mediated arthritis.
authors.affiliation: Departments of Experimental Immunology, Internal Medicine, and Genetics, Room K0-140, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. o.karpus@amc.uva.nl.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Karpus
authors.affiliation: Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, A-1090, Vienna, Austria. hans.kiener@meduniwien.ac.at.
authors.forename: Hans P
authors.initials: HP
authors.lastname: Kiener
authors.affiliation: Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, A-1090, Vienna, Austria. birgit.niederreiter@meduniwien.ac.at.
authors.forename: Birgit
authors.initials: B
authors.lastname: Niederreiter
authors.affiliation: Departments of Human Genetics and Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. a.s.yilmaz-elis@lumc.nl.
authors.forename: A Seda
authors.initials: AS
authors.lastname: Yilmaz-Elis
authors.affiliation: Departments of Human Genetics and Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. j.van_der_kaa@lumc.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: van der Kaa
authors.affiliation: Departments of Experimental Immunology, Internal Medicine, and Genetics, Room K0-140, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. v.ramaglia@amc.uva.nl.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ramaglia
authors.affiliation: Departments of Human Genetics and Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. r.arens@lumc.nl.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.affiliation: Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, A-1090, Vienna, Austria. josef.smolen@wienkav.at.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: Centre for Complement & Inflammation Research, Department of Medicine, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. m.botto@imperial.ac.uk.
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.affiliation: Departments of Experimental Immunology, Internal Medicine, and Genetics, Room K0-140, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. p.p.tak@amc.uva.nl.|GlaxoSmithKline Pharmaceuticals Research and Development, Gunnels Wood Road, Stevenage, SG1 2NY, UK. p.p.tak@amc.uva.nl.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Departments of Human Genetics and Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. j.s.verbeek@lumc.nl.
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.affiliation: Departments of Experimental Immunology, Internal Medicine, and Genetics, Room K0-140, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. j.hamann@amc.uva.nl.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000096:biosynthesis*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D018958:CD55 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D000936:Antigen-Antibody Complex; D018958:CD55 Antigens; D003094:Collagen