Type IX collagen deficiency enhances the binding of cartilage-specific antibodies and arthritis severity.
Joint cartilage is attacked in both autoimmune inflammatory and osteoarthritic processes. Type IX collagen (CIX) is a protein of importance for cartilage integrity and stability. In this study we have backcrossed a transgenic disruption of the col9a1 gene, which leads to an absence of CIX, into two different inbred mouse strains, DBA/1 and B10.Q. None of the CIX-deficient mice developed observable clinical or microscopic osteoarthritis, but DBA/1 male mice had more pronounced enthesopathic arthritis, the so-called stress-induced arthritis. Both DBA/1 and B10.Q strains are susceptible to the induction of collagen-induced arthritis, and CIX deficiency in both strains led to the development of a more severe arthritis than in the controls. Induction of arthritis with monoclonal antibodies against type II collagen (CII) led to an earlier arthritis in the paws that also involved the knee joints. The antibodies used, which were specific for the J1 and the C1I epitopes of CII, initiate their arthritogenic attack by binding to cartilage. The C1I-specific antibodies bound to cartilage better in CIX-deficient mice than in wild-type animals, demonstrating that the lack of CIX in cartilage leads to an increased accessibility of structures for antibody binding and thus making the joints more vulnerable to inflammatory attack. These findings accentuate the importance of cartilage stability; cartilage disrupted as a result of genetic disorders could be more accessible and vulnerable to an autoimmune attack by pathogenic antibodies.
Carlsen
Stefan
S
Medical Inflammation Research, BMC I11, Lund University, SE-221 84 Lund, Sweden.
Nandakumar
Kutty Selva
KS
Holmdahl
Rikard
R
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D001323:Autoantibodies / Q000276:immunology*; D002356:Cartilage / Q000276:immunology*; D003094:Collagen / Q000276:immunology; D024081:Collagen Type IX / Q000172:deficiency*; D004198:Disease Susceptibility; D000939:Epitopes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000209:etiology; D012720:Severity of Illness Index; D013314:Stress, Mechanical
D001323:Autoantibodies; D024081:Collagen Type IX; D000939:Epitopes; D003094:Collagen