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Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis
Jing Song, … , Eddie A. James, Jane H. Buckner
Jing Song, … , Eddie A. James, Jane H. Buckner
Published January 28, 2021
Citation Information: JCI Insight. 2021;6(5):e145217. https://doi.org/10.1172/jci.insight.145217.
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Research Article Immunology

Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis

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Abstract

Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC–specific T cells were also present among synovial fluid T cells and secreted IFN-γ. Two of these cit-TNC T cell epitopes were also recognized by antibodies within the serum and synovial fluid of individuals with RA. Detectable serum levels of cit-TNC–reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC–reactive antibodies were correlated with rheumatoid factor and elevated in subjects with a history of smoking. This work confirms cit-TNC as an autoantigen that is targeted by autoreactive CD4+ T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA.

Authors

Jing Song, Anja Schwenzer, Alicia Wong, Sara Turcinov, Cliff Rims, Lorena Rodriguez Martinez, David Arribas-Layton, Christina Gerstner, Virginia S. Muir, Kim S. Midwood, Vivianne Malmström, Eddie A. James, Jane H. Buckner

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Figure 6

Cit-TNC antibodies are associated with CCP seropositivity and the shared epitope.

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Cit-TNC antibodies are associated with CCP seropositivity and the shared...
Antibody responses to cit-TNC peptides or their arginine counterparts in serum from patients with RA and HC subjects were measured by ELISA. (A) cit-TNC17 and cit-TNC56 seropositivity was more prevalent in CCP+ RA subjects (n = 55) than CCP– RA subjects (n = 43). Each symbol represents an individual subject, and the horizontal line shows the median. Dotted lines indicate cut-off for positivity. Numbers below x axis indicate percentage of each cohort that were seropositive. Left panel, cit-TNC17; cut off AU = 29.51. Right panel, cit-TNC56; cut off AU = 91.98. P values were calculated using a Kruskal Wallis test with Dunn’s multiple comparison test (*P < 0.05 and ****P < 0.001). (B) Heatmaps showing cit-TNC antibody seropositivity and its association with the HLA shared epitope (SE) in CCP+ RA subjects (n = 72; Autoantibody Cohorts 1 and 2 combined) and CCP– RA patients (n = 43).

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