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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Relapsing polychondritis is an autoinumme 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 muMT 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.

Detaljer

Författare
  • AS Hansson
  • Martina Johannesson
  • Lars Svensson
  • KS Nandakumar
  • Dick Heinegård
  • Rikard Holmdahl
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)959-966
TidskriftAmerican Journal of Pathology
Volym164
Utgivningsnummer3
StatusPublished - 2004
PublikationskategoriForskning
Peer review utfördJa