Rat cytomegalovirus infection enhances type II collagen arthritis in rats

Smith, Charles B.; Griffiths, Marie; Wei, Lian S.

doi:10.1002/art.1780291012

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…This is an attractive hypothesis and earlier experiments showing that various interferon inducers prevent the development of adjuvant arthritis are compatible with such a possibility (Chang et al 1977). Interestingly, it has been demonstrated that CIA in rats is dramatically enhanced by an underlying cytomegalovirus infection (Smith et al 1986). Activation of arthritogenic T cells in vivo by the mimicry or adjuvanticity of endogenous infectious agents is a challenging possibility which needs further investigation.…”

Section: Adjuvant Arthritis and Spontaneous Arthritismentioning

confidence: 99%

Type II Collagen Autoimmunity in Animals and Provocations Leading to Arthritis

Holmdahl

Andersson

Goldschmidt

et al. 1990

Immunological Reviews

283

247

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Section: Adjuvant Arthritis and Spontaneous Arthritismentioning

confidence: 99%

Type II Collagen Autoimmunity in Animals and Provocations Leading to Arthritis

Holmdahl

Andersson

Goldschmidt

et al. 1990

Immunological Reviews

283

247

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“…For example, subsets of patients with a history of Salmonella infection develop reactive arthritis. Aggravation or exacerbation of arthritis induced by viral or bacterial infection in rheumatoid arthritis (RA) patients is a phenomenon sometimes observed clinically (3), and such aggravation of arthritis is also observed in rats (4). The cause of aggravation of arthritis has not yet been elucidated.…”

mentioning

confidence: 99%

Unmethylated oligo-DNA containing CpG motifs aggravates collagen-induced arthritis in mice

Miyata

Kobayashi

Sasajima

et al. 2000

Arthritis & Rheumatism

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Objective. To investigate the effects of an intra-dermal injection of an unmethylated oligodeoxynucleo-tide (ODN) containing CpG motifs on the severity of collagen-induced arthritis (CIA). Methods. CIA was induced in DBA/1 LacJ mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant followed 3 weeks later by immunization with CII in Freund's incomplete adjuvant (yielding CIA mice). Unmethylated ODN containing a CpG motif was injected intradermally into DBA/1 LacJ mice at a dosage of 20 g (yielding CpG-CIA mice) 1 week prior to the first immunization with CII. Unmeth-ylated ODN containing a GpC motif instead of a CpG motif and ODN containing a methylated CpG motif were used to produce controls (GpC-CIA mice and mCpG-CIA mice, respectively). After the second immunization with CII, arthritis scores were measured weekly up to the eighth week. At the eighth week, the mice were killed, histopathologic changes in the ankle joints were examined, and titers of interferon-(IFN) in the supernatants of splenocytes (1 10 7) stimulated in culture by CII for 3 days were determined by enzyme-linked immunosorbent assay. Results. CpG-CIA mice had significantly higher arthritis scores than CIA mice. CpG-CIA mice had more severe histopathologic changes than CIA mice and mCpG-CIA mice. Moreover, splenocytes in CpG-CIA mice produced higher IFN titers in response to CII than did splenocytes in CIA mice and mCpG-CIA mice. Conclusion. Injection of unmethylated oligo-DNA containing CpG motifs aggravated CIA through activation of the Th1-type immune response, suggesting that microbial infection could be one of the mechanisms for aggravation or exacerbation of arthritis or, alternatively , that such infection could be an adjuvant in the induction of arthritis in rheumatoid arthritis.

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Identification of a major antigenic epitope on CNBr‐fragment 11 of type II collagen recognized by murine autoreactive B cells

et al. 1991

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Immunization of certain strains of mice with native type II collagen (CII) induces both development of arthritis and an antibody response to autologous CII. The autoantibody response in a high-responder strain, the DBA/1 mouse, has been described earlier, and a number of monoclonal antibodies have been characterized for arthritogenicity and autoreactive binding to cartilage in vivo and in vitro. Here we map the antigenic epitope of one of these arthritogenic monoclonal antibodies (CII-C1). It belongs to a group of antibodies recognizing the CNBr fragment alpha 1(II)-CB11 of CII. Using the enzyme-linked immunosorbent assay technique, we show that the antibody reacts only with native, triplehelical CII, but not with other collagens. The antibody is able to stain specifically the CB11 fragment by immunoblotting, suggesting some partial renaturation of the CNBr fragment into triple-helical structures after blotting. The binding site of CII-C1 on CB11 was further focused by rotary shadowing of antibody-labeled CII to a site 89 +/- 8 nm from the amino end of CII, corresponding to the middle of CB11. This location was confirmed by cleavage of CB11 with trypsin, separation of the tryptic peptides by high-performance liquid chromatography and dot-blot analysis of the antigenic peptides with the CII-C1 antibody. Sequencing of the single positive peptide located the antigenic epitope within the sequence GFAGQAGPAGATGAPGRP (residues 316-333). Assuming 0.29 nm per residue, this corresponds to a position within 92-96.5 nm from NH2 terminal end of CII. Apart from glycine residues, which are not exposed on the triple-helical structure, only two amino acid residues (F-x-y-Q) are conserved in CII from different species but are not found in the triple-helix of other collagens except type IV collagen. Therefore, this structure is likely to be of critical importance for the binding of the CII-C1 antibody. Of potential importance is that this structure is also found in certain other arthritogenic proteins such as 65-kDa mycobacterial protein, in CMV and EBV.

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Rat cytomegalovirus infection enhances type II collagen arthritis in rats

Cited by 5 publications

References 23 publications

Type II Collagen Autoimmunity in Animals and Provocations Leading to Arthritis

Type II Collagen Autoimmunity in Animals and Provocations Leading to Arthritis

Unmethylated oligo-DNA containing CpG motifs aggravates collagen-induced arthritis in mice

Identification of a major antigenic epitope on CNBr‐fragment 11 of type II collagen recognized by murine autoreactive B cells

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