Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis

Arthritis Rheum. 1997 Jun;40(6):1115-25. doi: 10.1002/art.1780400616.


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.

Conclusion: 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.

MeSH terms

  • Adipokines
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Rheumatoid / immunology*
  • Autoantigens / immunology*
  • Cartilage / immunology
  • Chitinase-3-Like Protein 1
  • Clone Cells
  • Epitopes
  • Female
  • Glycoproteins / immunology*
  • Humans
  • Immune Tolerance
  • Lectins
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Peptides / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Adipokines
  • Autoantigens
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Epitopes
  • Glycoproteins
  • Lectins
  • Peptides