How can animal models be used to explain the autoimmune origins of relapsing polychondritis (RP)?

Updated: Dec 06, 2018
  • Author: Nicholas Compton, MD; Chief Editor: Herbert S Diamond, MD  more...
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Mouse and rat models have been helpful in elucidating the autoimmune origin of relapsing polychondritis. Immunization of rats with native bovine type II collagen resulted in bilateral auricular chondritis, with histologic findings similar to the findings of human relapsing polychondritis in 12 of 88 (14%) rats. In addition, 8 of 12 rats developed arthritis. Severe auricular chondritis was accompanied by immunofluorescence positive for IgG and C3 in affected cartilage and by circulating IgG that was reactive against native bovine type II collagen.

Immunization of a different strain of rats with native chick type II collagen was associated with auricular chondritis, in addition to the intended collagen-induced arthritis. Biopsy studies showed that the few auricular lesions contained IgG and C3. Antibodies to native type II collagen were found in the sera of rats that developed auricular chondritis and in rats with collagen-induced arthritis. [13]

Although most data implicate cartilage collagens as the immunogens in relapsing polychondritis, immunization of rats with matrilin 1, a noncollagenous cartilage matrix protein, is associated with development of a clinical syndrome resembling relapsing polychondritis. The syndrome differed significantly from the collagen immunization disease model in that the trachea, nasal cartilages, and kidneys primarily were affected, and the joints and auricles were spared. Matrilin 1 is found in highest levels in the tracheal cartilage and in the nasal septum, likely explaining the observed clinical differences. Matrilin 1 is also found in adult auricular cartilage and costochondral cartilage and is absent in articular cartilage. The presence of both humoral and cellular responses to matrilin 1 has been detected in a patient with significant involvement of the auricular, nasal, and tracheobronchial cartilage and with little arthritis. [14]

The same investigators demonstrated a crucial role for B cells and C5 in the induction of relapsing polychondritis–like symptoms. Additionally, pathogenicity of matrilin 1–specific antibodies in their matrilin 1–induced relapsing polychondritis mouse model was recently recognized. The authors note that further investigation is needed into the role of B cells, complement, and cell-mediated immunity to better understand this complex disease. [14]

Recently, transgenic mice that expressed HLA-DQ6a8b developed spontaneous polychondritis in middle age. This condition is characterized by auricular and nasal chondritis with polyarthritis. As opposed to mice with collagen type II–induced polychondritis, mice with spontaneous polychondritis do not show the overwhelming collagen type II immune response and may serve as a better animal model of relapsing polychondritis. [15]

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