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- Croxford, Allyson M., et al.
(author)
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Specific antibody protection of the extracellular cartilage matrix against collagen antibody-induced damage
- 2010
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In: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 62:11, s. 3374-3384
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The type II collagen (CII)-specific monoclonal antibodies (mAb) M2139 and CIIC1 induce arthritis in vivo and degrade bovine cartilage explants in vitro, whereas mAb CIIF4 is nonarthritogenic and prevents arthritis development when given in combination with M2139 and CIIC1. To determine the nature of the protective capacity of CIIF4 antibody, we examined the effects of adding CIIF4 to cartilage explants cultured in vitro with M2139 and CIIC1. METHODS: Bovine cartilage explants were cultured in the presence of M2139 and CIIC1, with or without CIIF4. Histologic changes were examined, and chemical changes to collagens and proteoglycans were assessed by Fourier transform infrared microspectroscopy (FTIRM). Fresh cartilage and cartilage that had been freeze-thawed to kill chondrocytes cultured with or without the addition of GM6001, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), were compared using FTIRM analysis. RESULTS: M2139 and CIIC1 caused progressive degradation of the cartilage surface and loss of CII, even in the absence of viable chondrocytes. CIIF4 did not cause cartilage damage, and when given with the arthritogenic mAb, it prevented their damage and permitted matrix regeneration, a process that required viable chondrocytes. Inhibition of MMP activity reduced cartilage damage but did not mimic the effects of CIIF4. CONCLUSION: CII-reactive antibodies can cause cartilage damage or can be protective in vivo and in vitro, depending on their epitope specificity. Since CII antibodies of similar specificity also occur in rheumatoid arthritis in humans, more detailed studies should unravel the regulatory mechanisms operating at the effector level of arthritis pathogenesis. © 2010 by the American College of Rheumatology.
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| 2. |
- Croxford, Allyson M., et al.
(author)
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Type II collagen-specific antibodies induce cartilage damage in mice independent of inflammation
- 2013
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In: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 65:3, s. 650-659
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Murine collagen antibody-induced arthritis (CAIA), like collagen-induced arthritis, has clinical and immunopathologic features that parallel those in human rheumatoid arthritis (RA). This study was undertaken to examine the effects of autoantibodies to type II collagen (CII) on articular cartilage in the paws of mice, under conditions in which other factors that may influence joint pathology could be excluded. METHODS: Mice of 2 different strains, B10.QC5delta and the parental strain B10.Q, were injected intravenously with either saline or arthritogenic monoclonal antibodies (mAb) to CII. B10.QC5delta mice lack complement factor C5 and do not develop CAIA when injected with arthritogenic mAb, whereas B10.Q mice have C5 and develop CAIA when administered the mAb and a subsequent injection of lipopolysaccharide. Three days after injection the paws of the mice were examined by standard histologic methods to assess morphologic appearance and proteoglycan loss, and by synchrotron-enhanced Fourier transform infrared microspectroscopy to assess chemical evidence of structural change. RESULTS: No macroscopic or microscopic signs of inflammation were evident in the mice. However, in contrast to the saline-injected controls, all mAb-injected mice exhibited cartilage damage in all joints, with loss of proteoglycans and collagen, chondrocyte hyperplasia and/or loss, and surface damage in the interphalangeal joints. CONCLUSION: The implication of these findings is that an autoimmune response to CII can disrupt articular cartilage, particularly that of the small joints, and the subsequent integrity of the cartilage depends on a balance between breakdown and repair. This has relevance with regard to RA, in which such autoantibodies occur but the inflammatory response may dominate clinically and mask underlying features of the autoimmune response. © 2013 by the American College of Rheumatology
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