Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis.

von Delwig, A., Locke, J., Robinson, J.H., Ng, W.F.
Journal   Arthritis Rheum.
Species  
Analytes Measured   IL-10 , IL-12 Total , IL-13 , IL-2 , IL-4 , IL-5
Matrix Tested   Peripheral blood mononuclear cell (PBMC) culture supernatants
Year   2010
Volume   62
Page Numbers   143-9
Application   Cytokines and Chemokines
Abstract

OBJECTIVE: 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.

METHODS: Peripheral blood mononuclear cells (PBMCs) from 28 RA patients and 18 healthy controls were stimulated with citrullinated or noncitrullinated aggrecan peptide Agg(84-103), and proliferative and cytokine responses were assessed using (3)H-thymidine incorporation assay, enzyme-linked immunosorbent assay, and intracellular cytokine analysis.

RESULTS: 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.

CONCLUSION: 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.

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CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-2 Kit
IL-2 | Non-human primate
Singleplex
V-PLEX NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-2 Kit
IL-2 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
Human IL-2 Antibody
IL-2
Human IL-4 Antibody
IL-4
Human IL-5 Antibody
IL-5
Human IL-10 Antibody
IL-10
Human IL-13 Antibody
IL-13
Mouse IL-2 Antibody
IL-2
Mouse IL-4 Antibody
IL-4
Mouse IL-5 Antibody
IL-5
Mouse IL-10 Antibody
IL-10
Rat IL-4 Antibody
IL-4
Rat IL-5 Antibody
IL-5
Rat IL-10 Antibody
IL-10
Rat IL-13 Antibody
IL-13
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