title: The occurrence of autoantibodies to matrilin 1 reflects a tissue-specific response to cartilage of the respiratory tract in patients with relapsing polychondritis.
abstract: OBJECTIVE
  Relapsing polychondritis (RP) is an inflammatory disease that mainly affects cartilage tissue in the auricle, nose, and lower respiratory tract. When tracheolaryngeal cartilage is involved, the disease is occasionally fatal. Matrilin 1 is a cartilage-specific protein most prominently expressed in tracheal cartilage, but not in joint cartilage. Immunization with the protein in rats and mice induces respiratory distress and nasal destruction, as seen in RP. We investigated the response to matrilin 1 and other cartilage proteins in sera from patients with RP, 4 additional groups of patients with other major connective tissue diseases, and healthy control subjects.
  
  
  METHODS
  Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) for antibody responses to matrilin 1, types II, IX, and XI collagen, and cartilage oligomeric matrix protein (COMP). Titers above the mean + 3SD of controls were considered positive. Specificity of matrilin 1 recognition was further investigated by the capacity of high-titer sera to block the binding of a matrilin 1-specific monoclonal antibody in inhibition ELISAs. In vivo reactivity and specificity were tested by injecting sera into neonatal mice, and antibody binding was detected by immunohistochemical staining.
  
  
  RESULTS
  Serum antibodies from RP patients bound tracheolaryngeal and nasal cartilage in vivo and inhibited the binding of anti-matrilin 1-specific monoclonal antibodies. Thirteen of the 97 RP patients had increased titers of matrilin 1 antibody. Positive titers correlated with respiratory symptoms in 69% of the cases. Significant responses to type II collagen and COMP were also detected.
  
  
  CONCLUSIONS
  Antibodies to matrilin 1 bind tracheolaryngeal cartilage in vivo and are correlated with an inflammatory attack on tracheolaryngeal cartilage that is often seen in RP.
authors.affiliation: Medical Inflammation Research, Lund University, 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: J C
authors.initials: JC
authors.lastname: Piette
authors.forename: H
authors.initials: H
authors.lastname: Burkhardt
authors.forename: R
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002356:Cartilage / Q000276:immunology / Q000503:physiopathology; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D051379:Mice; D008875:Middle Aged; D009928:Organ Specificity; D011081:Polychondritis, Relapsing / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D012137:Respiratory System / Q000276:immunology / Q000503:physiopathology
chemical_list: D001323:Autoantibodies; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577539:MATN1 protein, human; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; C577553:TSP5 protein, human