Class II major histocompatibility complex-associated response to type XI collagen regulates the development of
Jonatan Tuncel1, Sabrina Haag, Stefan Carlsén
1Karolinska Institute, Stockholm, Sweden.
Objective:
Chronic inflammation of the peripheral joints is a hallmark of rheumatoid arthritis (RA). The autoantibody response in RA has been shown to be directed mainly to ubiquitous antigens, whereas the response to cartilage proteins has been less extensively investigated. This study was undertaken to characterize the immune response in pristane-induced arthritis (PIA) in the rat to the cartilage-specific proteins type II collagen (CII) and type XI collagen (CXI) and to genetically fine-map their underlying major histocompatibility complex (MHC) associations.
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.
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Chronic Inflammation: Introduction
Hypersensitivity Reactions: Immune-Complex Reactions
Fibril-associated Collagen
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
The JAK-STAT Signaling Pathway


