Yeremenko, Nataliya and Haerle, Peter and Cantaert, Tineke and van Tok, Melissa and van Duivenvoorde, Leonie M. and Bosserhoff, Anja and Baeten, Dominique (2014) The cartilage protein melanoma inhibitory activity contributes to inflammatory arthritis. RHEUMATOLOGY, 53 (3). pp. 438-447. ISSN 1462-0324, 1462-0332
Full text not available from this repository. (Request a copy)Abstract
Objective. Melanoma inhibitory activity (MIA) is a small chondrocyte-specific protein with unknown function. MIA knockout mice (MIA(-/-)) have a normal phenotype with minor microarchitectural alterations of cartilage. Our previous study demonstrated that immunodominant epitopes of MIA are actively presented in an HLA-DR4-restricted manner in the inflamed RA joint. The objective of this study was to investigate the potential role of MIA as an autoantigen. Methods. Collagen-induced arthritis (CIA) and anti-collagen antibody-induced arthritis (CAIA) were induced in MIA(-/-) mice. Anti-type II collagen (anti-CII) antibodies were measured by ELISA. T cell proliferation and cytokine production were assessed by flow cytometry. Results. MIA(-/-) mice had a markedly reduced incidence and severity of CIA and CAIA compared with wild-type (WT) mice. Attenuation of disease was not related to defective binding of anti-CII antibodies to cartilage in the absence of MIA. However, MIA(-/-) mice had significantly reduced anti-CII IgG(1) and IgG(2a) antibody levels accompanied by an increase in FoxP3-expressing CD25(+)CD4(+) regulatory T cells. This was paralleled by a significant reduction in CII-specific IFN-gamma production by T cells in MIA(-/-) but not WT animals, suggesting a qualitative impact of MIA on the collagen-induced Th1 response. Furthermore, Ag-specific proliferation of T cells after restimulation with MIA in WT but not MIA(-/-) mice indicated the existence of MIA-specific T cells in the context of CIA. Conclusion. These data support a role for MIA as an autoantigen during arthritis development. Whether MIA can influence the balance of pathogenic vs regulatory responses in human RA remains to be investigated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLLAGEN-INDUCED ARTHRITIS; ACID-SENSITIVE PROTEIN; RAP-DEFICIENT MICE; RHEUMATOID-ARTHRITIS; MIA/CD-RAP; CHONDROCYTE DIFFERENTIATION; EXPRESSION; GLYCOPROTEIN-39; CELLS; MARKER; autoantigen; rheumatoid arthritis; collagen-induced arthritis; MIA; melanoma-inhibiting activity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Nov 2019 14:36 |
| Last Modified: | 18 Nov 2019 14:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10622 |
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