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: 2056

Citrullination Is Not a Determinant in the Lack of Tolerance to Peptidylarginine Deiminase 2 and 4 in Rheumatoid Arthritis

Pooja Naik1, Ryan Davis2, Jon T. Giles3, Felipe Andrade4 and Erika Darrah5, 1Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 2Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Columbia University, New York, NY, 4Medicine/Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 5Department of Medicine/Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: autoantibodies, autoantigens, citrullination and rheumatoid arthritis (RA), PAD

  • 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: Tuesday, October 23, 2018

Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster III

Session Type: ACR Poster Session C

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

Background/Purpose: Peptidylarginine deiminase (PAD) 2 and 4 are targets of the humoral response in RA. However, the mechanisms by which these enzymes become immunogenic in this disease are still unknown. In addition of catalyzing the conversion of arginine residues to citrulline in a broad range of substrates, these enzymes also autocitrullinate. Since citrullination is a major determinant in the lack of tolerance to autoantigens in RA, we investigated whether PAD2 and PAD4 may also be part of the anti-citrullinated protein autoantibody (ACPA) response in this disease.

Methods: We determined the prevalence of antibodies against auto-citrullinated PAD2 and PAD4 in 184 patients with established RA. ELISA assays were developed to screen sera from RA patients and healthy controls for reactivity to native and citrullinated PADs. Antibody binding to native and citrullinated PADs was compared and confirmed in blocking experiments. Recognition of native vs. citrullinated PAD at the individual level was plotted and analyzed by linear regression.

Results: Anti-native PAD4 and anti-native PAD2 antibodies were present in 42% and 18.5% of patients in the cohort, respectively. Autoantibodies against PAD4 bound similarly to both the native and citrullinated form such that anti-PAD4 levels against the citrullinated form positively correlated with that against the native form (R square = 0.863; p = <0.0001). Only two sera were identified that bound exclusively to citrullinated PAD4. Similar results were obtained for binding of autoantibodies to the native and citrullinated forms of PAD2 (R square = 0.908; p = <0.0001), with only four sera exclusively binding to citrullinated PAD2. Pre-incubation of sera with native PAD4 or PAD2 in solution significantly reduced antibody binding to the respective citrullinated protein (p ≤ 0.0001).

Conclusion: Taken together, this study demonstrates that citrullination is not a major determinant in the breech of tolerance to PAD2 and PAD4 in RA. Although PADs are necessary for the production of ACPAs, the data suggest that anti-PAD autoantibodies and ACPAs are likely driven by distinct pathogenic mechanisms.


Disclosure: P. Naik, None; R. Davis, None; J. T. Giles, None, 7; F. Andrade, Medimmune; Pfizer; BMS, 2, 5, 7; E. Darrah, Medimmune, Pfizer, Padlock Therapeutics,, 2, 5, 7.

To cite this abstract in AMA style:

Naik P, Davis R, Giles JT, Andrade F, Darrah E. Citrullination Is Not a Determinant in the Lack of Tolerance to Peptidylarginine Deiminase 2 and 4 in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/citrullination-is-not-a-determinant-in-the-lack-of-tolerance-to-peptidylarginine-deiminase-2-and-4-in-rheumatoid-arthritis/. 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 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/citrullination-is-not-a-determinant-in-the-lack-of-tolerance-to-peptidylarginine-deiminase-2-and-4-in-rheumatoid-arthritis/

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