Rheumatoid Arthritis Basic Science Studies
Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis
Article first published online: 28 DEC 2009
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 1, pages 143–149, January 2010
How to Cite
von Delwig, A., Locke, J., Robinson, J. H. and Ng, W.-F. (2010), Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis. Arthritis & Rheumatism, 62: 143–149. doi: 10.1002/art.25064
- Issue published online: 28 DEC 2009
- Article first published online: 28 DEC 2009
- Manuscript Accepted: 25 SEP 2009
- Manuscript Received: 6 JUL 2009
- Arthritis Research Campaign. Grant Numbers: 17864, 14912
Rheumatoid arthritis (RA) is considered to be a prototypical autoimmune disease. However, the autoantigens that play an important role in the development of RA remain unclear. The aim of this study was to investigate whether T cells specific for citrullinated epitopes from self proteins are present in patients with RA.
Peripheral blood mononuclear cells (PBMCs) from 28 RA patients and 18 healthy controls were stimulated with citrullinated or noncitrullinated aggrecan peptide Agg84–103, and proliferative and cytokine responses were assessed using 3H-thymidine incorporation assay, enzyme-linked immunosorbent assay, and intracellular cytokine analysis.
A proliferative response to the citrullinated aggrecan peptide was detected in >60% of RA patients but not in healthy controls. Furthermore, citrullinated aggrecan peptide–stimulated PBMCs from RA patients produced high levels of the proinflammatory cytokine interleukin-17 (IL-17), accompanied by an induction of IL-17+CD4+ T cells. In contrast, PBMCs from RA patients and healthy controls exhibited no response to stimulation with the noncitrullinated aggrecan peptide.
Proinflammatory T cell responses to stimulation with a citrullinated arthritogenic aggrecan peptide were detected in RA patients but not in healthy individuals, suggesting a role for these autoantigen-specific T cells in the pathogenesis of RA. Our results suggest that the lack of response to the noncitrullinated analog peptide not only implicates the citrulline residue in T cell recognition but also highlights the potential value of citrullinated aggrecan peptide–specific responses as biomarkers of RA. To our knowledge, this is the first study to demonstrate the presence of citrullinated antigen–specific T cells in human RA.