title: Complement deficiency ameliorates collagen-induced arthritis in mice.
abstract: Collagen-induced arthritis (CIA) is an experimental animal model of human rheumatoid arthritis being characterized by synovitis and progressive destruction of cartilage and bone. CIA is induced by injection of heterologous or homologous collagen type II in a susceptible murine strain. DBA/1J mice deficient of complement factors C3 (C3(-/-)) and factor B (FB(-/-)) were generated to elucidate the role of the complement system in CIA. When immunized with bovine collagen type II emulsified in CFA, control mice developed severe arthritis and high CII-specific IgG Ab titers. In contrast, the C3(-/-) and FB(-/-) were highly resistant to CIA and displayed decreased CII-specific IgG Ab response. A repeated bovine collagen type II exposure 3 wk after the initial immunization led to an increase in the Ab response in all mice and triggered arthritis also in the complement-deficient mice. Although the arthritic score of the C3(-/-) mice was low, the arthritis in FB(-/-) mice ranked intermediate with regard to C3(-/-) and control mice. We conclude that complement activation by both the classical and the alternative pathway plays a deleterious role in CIA.
authors.affiliation: Department of Medical Biochemistry, Göteborg University, Göteborg, Sweden.
authors.forename: Max Albert
authors.initials: MA
authors.lastname: Hietala
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleinau
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
mesh_terms: D000483:Alleles; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology; D002358:Cartilage, Articular / Q000276:immunology / Q000473:pathology; D002417:Cattle; D024043:Collagen Type II / Q000008:administration & dosage* / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics; D011415:Complement Factor B / Q000172:deficiency* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic
chemical_list: D024043:Collagen Type II; D003176:Complement C3; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007074:Immunoglobulin G; D011415:Complement Factor B