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Rheumatology 2000; 39: 1326-1331
© 2000 British Society for Rheumatology

Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions

K. Vos1, A. M. M. Miltenburg4, K. E. van Meijgaarden2, M. van den Heuvel4, D. G. Elferink2, P. J. M. van Galen4, R. A. van Hogezand3, E. van Vliet-Daskalopoulou4, T. H. M. Ottenhoff2, F. C. Breedveld1, A. M. H. Boots4 and R. R. P. de Vries2

1 Departments of Rheumatology,
2 Immunohaematology and Blood Bank and
3 Hepato-Gastroenterology, Leiden University Medical Center, Leiden and
4 Department of Pharmacology, Section Immunology, NV Organon, Oss, The Netherlands

Objective. To study the specificity of the peripheral blood mononuclear cell (PBMC) response to peptides derived from human cartilage glycoprotein-39 (HC gp-39) in patients with rheumatoid arthritis (RA) and the correlation between this response and disease activity.

Methods. RA patients, patients with systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) or osteoarthritis (OA) and healthy controls were studied. All individuals were typed for HLA-DRB1 and their disease activity score was documented. Proliferation of PBMC was measured following incubation with five different HC gp-39-derived peptides, selected by the use of a DR4 (DRB1*0401) binding motif.

Results. A proliferative response to one of the five peptides (peptide 259–271 at 10 µg/ml) was more often observed in RA patients than in healthy controls (P=0.001). RA patients who expressed DRB1*0401 more often showed a response against this peptide than RA patients who did not express this RA-associated haplotype. This response was not RA-specific since patients with IBD or OA also showed a response significantly more frequently than healthy controls (P=0.02 and P=0.03 respectively). However, the level of the response against peptide 259–271 correlated with disease activity in RA patients but not in patients with IBD or SLE. Increased responses to HC gp-39 263-275 were found in patients with IBD or OA; a trend towards such a response failed to reach significance in RA patients in this study.

Conclusion.  In RA patients as well as in patients with other inflammatory conditions, HC gp-39-derived peptides may be targets of the T-cell-mediated immune response. In the RA patient group the immune response to HC gp-39-derived peptide 259–271 correlated with disease activity.

KEY WORDS: Rheumatoid arthritis, YKL-40, Human cartilage glycoprotein-39, Cellular response, T cells, Autoantigen.

Correspondence to: K. Vos, Department of Rheumatology, C4-R, Leiden University Medical Center, P. O. Box, 9600, 2300 RC Leiden, The Netherlands.


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