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Relapsing polychondritis, induced in mice with matrilin 1, is an antibody- and complement-dependent disease.

Abstract
Relapsing polychondritis is an autoimmune disease that affects cartilage in the ear, nose, and respiratory tract. A pathogenic immune response has been proposed and antibodies to several cartilage proteins are detected in sera from these patients. To investigate the role of the humoral immune response in relapsing polychondritis, we used the matrilin-1-induced relapsing polychondritis model. Mice deficient of B cells (muMT) and mice congenic at the complement factor 5, were immunized with matrilin-1, a cartilage-specific protein mainly detected in the tracheal cartilage. To investigate the binding properties and tissue selection of matrilin-1-specific antibodies we produced matrilin-1-specific B-cell hybridomas. Although 83% of the micro MT heterozygous mice developed respiratory distress and erosive chondritis in the respiratory tract, none of the B-cell-deficient mice were susceptible to disease. In addition, we show that complement factor 5 is important for the induction of matrilin-1-induced relapsing polychondritis. Monoclonal matrilin-1-specific antibodies injected into neonatal mice bound specifically to cartilage of the respiratory tract and adult B-cell-deficient mice injected with the same antibodies developed erosive chondritis in the respiratory tract. We conclude that relapsing polychondritis can be mediated by a pathway involving tissue-specific antibodies and complement activation.
AuthorsAnn-Sofie Hansson, Martina Johannesson, Lars Svensson, Kutty Selda Nandakumar, Dick Heinegård, Rikard Holmdahl
JournalThe American journal of pathology (Am J Pathol) Vol. 164 Issue 3 Pg. 959-66 (Mar 2004) ISSN: 0002-9440 [Print] United States
PMID14982849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • Complement C5
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Matn1 protein, mouse
  • Matrilin Proteins
Topics
  • Animals
  • Animals, Newborn
  • Antibodies
  • Autoimmune Diseases (immunology, pathology)
  • B-Lymphocytes (immunology)
  • Cartilage (immunology, pathology)
  • Complement C5 (immunology)
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins (immunology, toxicity)
  • Glycoproteins (immunology, toxicity)
  • Hybridomas
  • Matrilin Proteins
  • Mice
  • Mice, Congenic
  • Polychondritis, Relapsing (chemically induced, immunology)
  • Respiratory System (immunology)

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