Abstract | OBJECTIVE: METHODS: The genetic control of CII and CXI immunity was mapped using intra-MHC-recombinant inbred strains immunized with the respective collagens. Reactivity with CII and CXI was tested in acute and chronic PIA and in 356 HLA-typed patients with recently diagnosed RA. RESULTS: Mapping of arthritis susceptibility within the MHC region revealed a 144-223-kb locus containing <12 genes, including paralogs for HLA-DQ and HLA-DR. Susceptibility to CII and CXI was linked to haplotypes RT1(av1) (DA) and RT1(f) (DA.1F), respectively. After injection of pristane, rats of both strains developed weak T cell and IgG responses to CII, but not to CXI. In chronic arthritis, however, collagen reactivity was stronger, specific for CXI, and restricted to rats with RT1(f) MHC. Among RA patients, 12% exhibited a specific IgG response to CXI, 6% to CII, and 6% to both collagens. CONCLUSION: These findings demonstrate a shift in cartilage recognition in early and chronic arthritis in the rat, suggesting that CXI autoreactivity contributes to the perpetuation of chronic disease. The results provide evidence of the importance of joint antigens in arthritis development.
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Authors | Jonatan Tuncel, Sabrina Haag, Stefan Carlsén, Anthony C Y Yau, Shemin Lu, Harald Burkhardt, Rikard Holmdahl |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 64
Issue 8
Pg. 2537-47
(Aug 2012)
ISSN: 1529-0131 [Electronic] United States |
PMID | 22391806
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 by the American College of Rheumatology. |
Chemical References |
- Biomarkers
- Collagen Type XI
- Histocompatibility Antigens Class II
- Immunoglobulin G
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Amino Acid Sequence
- Animals
- Arthritis
(blood, etiology, immunology)
- Biomarkers
(blood)
- Case-Control Studies
- Chronic Disease
- Collagen Type XI
(immunology)
- Disease Models, Animal
- Disease Susceptibility
(immunology)
- Female
- Histocompatibility Antigens Class II
(analysis, blood)
- Humans
- Immunoglobulin G
(blood)
- Major Histocompatibility Complex
(immunology)
- Male
- Middle Aged
- Molecular Sequence Data
- Rats
- Rats, Inbred Strains
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