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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. https://doi.org/10.1172/jci.insight.145217.
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Research In-Press Preview Immunology

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

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Abstract

Tenascin-C, an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis. In this study, we utilized a systematic discovery process and identified five novel citrullinated tenascin-C (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with rheumatoid arthritis and showed signs of activation. Cit-TNC-specific T cells were also present among synovial fluid T cells and secreted interferon-γ. Two of these cit-TNC peptides were 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. Taken together 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 suggest that a unique set of epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of rheumatoid arthritis.

Authors

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

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