title: A new animal model for relapsing polychondritis, induced by cartilage matrix protein (matrilin-1).
abstract: Relapsing polychondritis (RP) differs from rheumatoid arthritis (RA) in that primarily cartilage outside diarthrodial joints is affected. The disease usually involves trachea, nose, and outer ears. To investigate whether the tissue distribution of RP may be explained by a specific immune response, we immunized rats with cartilage matrix protein (matrilin-1), a protein predominantly expressed in tracheal cartilage. After 2-3 weeks, some rats developed a severe inspiratory stridor. They had swollen noses and/or epistaxis, but showed neither joint nor outer ear affection. The inflammatory lesions involved chronic active erosions of cartilage. Female rats were more susceptible than males. The disease susceptibility was controlled by both MHC genes (f, l, d, and a haplotypes are high responders, and u, n, and c are resistant) and non-MHC genes (the LEW strain is susceptible; the DA strain is resistant). However, all strains mounted a pronounced IgG response to cartilage matrix protein. The initiation and effector phase of the laryngotracheal involvement causing the clinical symptoms were shown to depend on alphabeta T cells. Taken together, these results represent a novel model for RP: matrilin-1-induced RP. Our findings also suggest that different cartilage proteins are involved in pathogenic models of RP and RA.
authors.affiliation: Section for Medical Inflammation Research, Department of Cell and Molecular Biology, Lund University, 22362 Lund, Sweden. Ann-Sofie.Hansson@inflam.lu.se
authors.forename: A S
authors.initials: AS
authors.lastname: Hansson
authors.forename: D
authors.initials: D
authors.lastname: Heinegård
authors.forename: R
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002356:Cartilage / Q000276:immunology / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D004431:Ear, External / Q000276:immunology / Q000473:pathology; D004844:Epistaxis / Q000209:etiology; D016326:Extracellular Matrix Proteins / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000276:immunology*; D006239:Haplotypes / Q000235:genetics; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007817:Laryngeal Cartilages / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex; D008297:Male; D064235:Matrilin Proteins; D009300:Nasal Septum / Q000276:immunology / Q000473:pathology; D011081:Polychondritis, Relapsing / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012135:Respiratory Sounds / Q000209:etiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014132:Trachea / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D064235:Matrilin Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta