ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0775

T and B Cell Responses to Common Tenascin-C Peptides in RA

JING Song1, Anja Schwenzer2, Sara Turcinov3, Alicia Wong2, Cliff Rims1, Lorena Rodriguez Martinez2, David Arribas-Layton4, Christina Gerstner5, Virginia Muir6, Jeffrey Carlin7, Kim Midwood2, Vivianne Malmström8, Eddie James1 and Jane Buckner1, 1Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, 2Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom, 3Division of Rheumatology, Department of Medicine,Center for Molecular Medicine, Institutet, Stockholm, Sweden, 4Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, 5Division of Rheumatology, Department of Medicine,Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden, 6Center for Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, 7Department of Rheumatology, Virginia Mason Medical Center, Seattle, WA, 8Karolinska Institutet, Stockholm, Stockholms Lan, Sweden

Meeting: ACR Convergence 2020

Keywords: Autoantibody(ies), autoantigens, B-Cell Targets, rheumatoid arthritis, T Cell

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Saturday, November 7, 2020

Title: RA – Etiology & Pathogenesis Poster

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Although autoreactive CD4+ T cell and antibody responses against citrullinated antigens are known to contribute to loss of immune tolerance in rheumatoid arthritis (RA), identifying the immunodominant antigens remains an important priority.  In this study, we focused on tenascin-C, an extracellular matrix protein with proinflammatory properties, based on our previous studies reporting the presence of autoantibodies targeting a citrullinated epitope in the fibrinogen-like globe of tenascin-C in patients with established RA and patients with early synovitis. Here, we extend these findings utilizing a systematic discovery approach to identify novel citrullinated tenascin C epitopes that elicit T and B cell responses in patients with RA.

Methods: An algorithm was used to predict HLA-DRB1*0401 restricted epitopes along the entire length of the tenascin-C monomer. Predicted epitopes were then tested for their ability to bind HLA-DRB1*0401 and to elicit a T cell response in vitro. Multiplex HLA class II tetramer staining combined with cell surface marker antibodies was used to assess the frequency and phenotype of T cells specific for the immunogenic citrullinated-tenascin-C peptides in peripheral blood. Fluorospot assays were used to measure cytokines produced by synovial fluid mononuclear cells in response to citrullinated-tenascin-C peptides. Antibodies to citrullinated-tenascin-C peptides were detected in sera and synovial fluid using ELISAs and an extracellular matrix peptide microarray. The relationship between antibody seropositivity and clinical variables was modeled using logistic regression models with age and sex as co-variates. All RA subjects met the 2010 American College of Rheumatology criteria, and ACPA positivity was determined based on clinical testing for CCP.

Results: We identified five novel citrullinated-tenascin-C epitopes that were restricted by HLA-DRB1*0401. Notably, CD4 T cells specific for these epitopes were increased in the peripheral blood of patients with RA compared to healthy control subjects, and were present in synovial fluid. Furthermore, two of these citrullinated tenascin-C epitopes were also B cell epitopes that were recognized by antibodies in sera and synovial fluid from RA subjects. Strikingly, antibodies were present in 75% of the patients for one of these epitopes. Serum levels of these citrullinated-tenascin-C reactive antibodies were associated with rheumatoid factor, CCP seropositivity, the shared epitope, and smoking.

Conclusion: Taken together this work demonstrates the importance of citrullinated-tenascin C as an autoantigen in 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 RA.


Disclosure: J. Song, None; A. Schwenzer, None; S. Turcinov, None; A. Wong, None; C. Rims, None; L. Rodriguez Martinez, None; D. Arribas-Layton, None; C. Gerstner, None; V. Muir, Janssen, 3; J. Carlin, None; K. Midwood, None; V. Malmström, Pfizer, 2; E. James, Pfizer, 2, Janssen, 2, Sanofi, 2, Novartis, 2; J. Buckner, Bristol-Myers Squibb, 2, 5, Janssen, 2.

To cite this abstract in AMA style:

Song J, Schwenzer A, Turcinov S, Wong A, Rims C, Rodriguez Martinez L, Arribas-Layton D, Gerstner C, Muir V, Carlin J, Midwood K, Malmström V, James E, Buckner J. T and B Cell Responses to Common Tenascin-C Peptides in RA [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/t-and-b-cell-responses-to-common-tenascin-c-peptides-in-ra/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/t-and-b-cell-responses-to-common-tenascin-c-peptides-in-ra/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology