title: The cartilage protein melanoma inhibitory activity contributes to inflammatory arthritis.
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 IgG1 and IgG2a 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-γ 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. d.l.baeten@amc.uva.nl.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Yeremenko
authors.forename: Peter
authors.initials: P
authors.lastname: Härle
authors.forename: Tineke
authors.initials: T
authors.lastname: Cantaert
authors.forename: Melissa
authors.initials: M
authors.lastname: van Tok
authors.forename: Leonie M
authors.initials: LM
authors.lastname: van Duivenvoorde
authors.forename: Anja
authors.initials: A
authors.lastname: Bosserhoff
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D003094:Collagen / Q000009:adverse effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001324:Autoantigens; D016207:Cytokines; D016326:Extracellular Matrix Proteins; C513263:Mia protein, mouse; D003094:Collagen
keywords: MIA; autoantigen; collagen-induced arthritis; melanoma-inhibiting activity; rheumatoid arthritis