A new animal model for relapsing polychondritis, induced by cartilage matrix protein (matrilin-1)

Relapsing polychondritis (RP) differs from rheumatoid arthritis (RA) in tha t 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, w e immunized rats with cartilage matrix protein (matrilin-1), a protein pred ominantly expressed in tracheal cartilage. After 2-3 weeks, some rats devel oped a severe inspiratory strider. 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 susce ptible than males. The disease susceptibility was controlled by both MHC ge nes (f, 1, d, and a haplotypes are high responders, and u, n, and c are res istant) and non-MHC genes (the LEW strain is susceptible; the DA strain is resistant). However, all strains mounted a pronounced IgG response to carti lage matrix protein. The initiation and effector phase of the laryngotrache al involvement causing the clinical symptoms were shown to depend on alpha beta T cells. Taken together, these results represent a never model for RP: matrilin-1-induced RP. Our findings also suggest that different cartilage proteins are involved in pathogenic models of RP and RA.