| First Author | Myers LK | Year | 2004 |
| Journal | Arthritis Rheum | Volume | 50 |
| Issue | 9 | Pages | 3004-11 |
| PubMed ID | 15457470 | Mgi Jnum | J:159602 |
| Mgi Id | MGI:4452069 | Doi | 10.1002/art.20491 |
| Citation | Myers LK, et al. (2004) Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis. Arthritis Rheum 50(9):3004-11 |
| abstractText | OBJECTIVE: Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII(256-276)(N(263), D(266)), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis. METHODS: Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F(263) to N and E(266) to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII). RESULTS: The mutant rCII(N(263), D(266)) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII(256-276)(N(263), D(266)). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N(263), D(266)). Administration of rCII(N(263), D(266)) was ineffective in suppressing arthritis in IL4(-/-) mice, suggesting that the profound suppressive effects of rCII(N(263), D(266)) were mediated through the production of interleukin-4. CONCLUSION: These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII. |
