| 1. |
- Bajtner, Estelle, et al.
(författare)
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Chronic development of collagen-induced arthritis is associated with arthritogenic antibodies against specific epitopes on type II collagen
- 2005
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 7, s. R1148-R1157
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies against type II collagen (CII) are important in the development of collagen-induced arthritis (CIA) and possibly also in rheumatoid arthritis. We have determined the fine specificity and arthritogenicity of the antibody response to CII in chronic relapsing variants of CIA. Immunization with rat CII in B10.Q or B10.Q(BALB/cxB10.Q)F2 mice induces a chronic relapsing CIA. The antibody response to CII was determined by using triple-helical peptides of the major B cell epitopes. Each individual mouse had a unique epitope-specific response and this epitope predominance shifted distinctly during the course of the disease. In the B10.Q mice the antibodies specific for C1 and U1, and in the B10.Q(BALB/cxB10.Q)F2 mice the antibodies specific for C1, U1 and J1, correlated with the development of chronic arthritis. Injection of monoclonal antibodies against these epitopes induced relapses in chronic arthritic mice. The development of chronic relapsing arthritis, initially induced by CII immunization, is associated with an arthritogenic antibody response to certain CII epitopes.
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| 2. |
- Lange, F, et al.
(författare)
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Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ. - 1468-2060 .- 0003-4967. ; 64:4, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the mode of action of methotrexate (MTX) in different types of models for rheumatoid arthritis (RA) and multiple sclerosis (MS). Methods: Models for RA and MS were selected known to have different pathogenesis - that is, fibroblast induced arthritis in SCID mice, collagen induced arthritis (CIA), anticollagen II antibody induced arthritis (CAIA), and experimental autoimmune encephalomyelitis (EAE) in (Balb/c x B10.Q)F1 and B10.Q mice, and Pristane induced arthritis in DA rats (PIA). The MTX treatment was started 1 day after the onset of disease and continued for 14 days to compare effects on the different models. critically dependent on T cell activation (CIA, PIA, and EAE) were Results: All models known to be effectively down regulated by titrated doses of MTX. In contrast, no effects were seen on fibroblast induced arthritis or CAIA. No effects were seen on the levels of anticollagen 11 antibodies in the CIA experiment. Conclusion: The data show that MTX has strong ameliorative effect on both classical models of RA, like CIA and PIA, but also on a model for MS, EAE. It also suggests that MTX operates only in diseases which are preceded by, and dependent on, T cell activation. A comparison of CAIA and CIA suggested that MTX operates independently of arthritogenic antibodies. These results demonstrate that different animal models reflect the complexity of the corresponding human diseases and suggest that several models should be used for effective screening of new therapeutic agents.
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| 3. |
- Nandakumar, Kutty Selva, 1965-, et al.
(författare)
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Arthritogenic antibodies specific for a major type II collagen triple-helical epitope bind and destabilize cartilage independent of inflammation
- 2008
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 58:1, s. 184-196
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the significance and pathogenic potential of a highly conserved major type II collagen triple-helical epitope-specific antibody (U1; amino acids 494-504) in vivo and in vitro in patients with early rheumatoid arthritis (RA) and in experimental animal models of collagen-induced arthritis (CIA). METHODS: U1-specific antibodies in sera from patients with early RA (with or without joint erosions) were analyzed. Disease progression in the CIA models in mice and rats with anti-U1 antibodies was compared. The pathogenicity of binding of monoclonal antibodies (mAb) UL1 and CIIF4 to the U1 epitope and the F4 epitope (aa 926-936), respectively, was compared in vivo and on chondrocyte cultures and preformed cartilage in vitro, using Fourier transform infrared microspectroscopy analysis. In addition, UL1-induced proteoglycan depletion in vivo in the presence and absence of the complement factor C5 was analyzed. RESULTS: Increased levels of U1 antibodies were observed in patients with early RA, especially in association with joint erosions. A significant correlation of U1-specific antibodies with disease progression was found in rats and mice with CIA. UL1 mAb induced, whereas CIIF4 mAb inhibited, the progression of arthritis. Similarly, UL1, but not CIIF4, impaired matrix synthesis on chondrocyte cultures and adversely affected preformed cartilage. Furthermore, UL1 induced significant proteoglycan depletion in vivo 3 days after injection, even in the absence of C5. CONCLUSION: Antibody epitope specificity contributes significantly to the development of arthritis, and the early pathogenic events operate independent of inflammation both in vitro and in vivo.
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| 6. |
- Uysal, Hüseyin, et al.
(författare)
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Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis
- 2009
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Ingår i: Journal of Experimental Medicine. - New York, NY : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 206:2, s. 449-462
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII is indeed citrullinated in vivo. The structure determination of a Fab fragment of one of these antibodies in complex with a citrullinated peptide showed a surprising beta-turn conformation of the peptide and provided information on citrulline recognition. Based on these findings, we propose that autoimmunity to CII, leading to the production of antibodies specific for both native and citrullinated CII, is an important pathogenic factor in the development of RA.
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| 7. |
- Verdrengh, M, et al.
(författare)
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Total abrogation of collagen II-induced arthritis and the B cell response to type II collagen using suboptimal doses of a topoisomerase II antagonist.
- 2002
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:9, s. 829-831
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages. OBJECTIVE: To assess the impact of etoposide, a topoisomerase II antagonist known to induce monocyte apoptosis, on the development of CIA. METHODS: Mice were primed and booster immunised against collagen II (CII). One group of mice was treated with etoposide two days before CII immunisation and then on four consecutive days weekly until the end of the experiment. The second group of mice was injected with etoposide on four consecutive days a week starting 40 days after CII priming. The third group of mice were controls receiving phosphate buffered saline (PBS). The mice were examined for development of arthritis, numbers of circulating leucocytes, serum CII antibody, and cytokine concentrations. RESULTS: None of the mice given etoposide before CII immunisation developed arthritis. Serum concentrations of anti-CII antibodies were undetectable in these mice, whereas they displayed significantly increased concentrations of interferon gamma and interleukin 6. In addition, the CII specific B cell responses in the draining lymph nodes were highly suppressed. Also, mice treated with etoposide at the onset of clinical arthritis showed reduced frequency of their disease by 50%. CONCLUSION: There was a striking disease alleviating impact of topoisomerase II antagonist on the course of CII-induced arthritis.
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