Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis.
OBJECTIVE
To identify a cartilage-derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process.


METHODS
A DR4 (DRB1*0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein-39 (HC gp-39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RA-associated DR4 (DRB1*0401) molecules. High-affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp-39, the protein was injected into BALB/c mice.


RESULTS
HC gp-39-derived motif-based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen-specific T cells and to suppression of HC gp-39-induced arthritis.


CONCLUSIONS
These data indicate that HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a candidate for antigen-specific immunotherapy.
Verheijden
G F
GF
NV Organon, Oss, The Netherlands.
Rijnders
A W
AW
Bos
E
E
Coenen-de Roo
C J
CJ
van Staveren
C J
CJ
Miltenburg
A M
AM
Meijerink
J H
JH
Elewaut
D
D
de Keyser
F
F
Veys
E
E
Boots
A M
AM
D054392:Adipokines; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002356:Cartilage / Q000276:immunology; D000071451:Chitinase-3-Like Protein 1; D002999:Clone Cells; D000939:Epitopes; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D037102:Lectins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D054392:Adipokines; D001324:Autoantigens; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D000939:Epitopes; D006023:Glycoproteins; D037102:Lectins; D010455:Peptides