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: 1979

Rheumatoid Arthritis-Associated Genetic Alteration Defines a New Promoter for Peptydil Arginine Deiminase 4 Gene

Daniel M. Tóth1, Timea Ocskó2, Tibor T. Glant1 and Tibor A. Rauch1, 1Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, 2Orthopedic Surgery, Rush University Medical Center, Chicago, IL

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Rheumatoid arthritis (RA)

  • 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: Genetics, Genomics and Proteomics Poster

Session Type: ACR Poster Session C

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

Background/Purpose: Anti-citrullinated protein antibodies (ACPA) are frequently detected in Rheumatoid Arthritis (RA) patients and used as diagnostic biomarkers at a very early stage of the disease. ACPAs are raised against various peptide epitopes carrying citrullinated arginines generated by peptidyl arginine deiminase (PADI) enzyme family members. PADI4 gene is highly expressed in neutrophils in peripheral blood and also known to citrullinate histone proteins. RA-associated PADI4 single nucleotide polymorphisms (SNPs) do not alter amino acid composition; therefore, it is challenging to explore how they can contribute to RA pathology. We investigated the effect of SNP rs2240335 on transcriptional regulation of PADI4 gene.

Methods: We have investigated the epigenetic landscape of the human chromosome region harboring the PADI4 gene and focused on histone modifications that predict active promoters. Using 5’RACE method we explored alternative isoform-encoding transcript of PADI4 gene. Quantitative reverse transcription PCR was used to explore isoform expression in human tissues. Cellular distribution of a novel short PADI4 isoform was studied by confocal fluorescence microscopy. Short PADI4 isoform’s potential catalytic function was tested using in vitro transcription and translation system. The disease-associated SNP’s effect on transcription was assessed in transient expression studies.

Results: Epigenetic profile analysis around the PADI4 gene revealed a new promoter region, which proved to be active on bone marrow. We cloned and sequenced the corresponding transcript and designated PADI4-ΔN. PADI4-ΔN is a truncated isoform that only encodes the C-terminal catalytic domain of the enzyme, which is highly expressed in bone marrow sample and neutrophils. PADI4-ΔN was fused to red fluorescent protein (RFP) and overexpressed in cells. Confocal microscopic studies detected the RFP:PADI4-ΔN in cytoplasmic region and nuclei of the transfected cells. Studies addressed to reveal catalytic activity of PADI4-ΔN could not detect any enzymatic activity in vitro assays. Transient expression studies revealed that the two allele variants (i.e., G or T at rs2240335 position) can contribute differently to the novel PADI4 promoter activity, which is ultimately reflected by Luciferase activity in cell lysates.

Conclusion: The PADI4 gene encodes at least three isoforms: (i) the well-characterized full-length isoform, (ii) a C-terminus deleted (PADI4-ΔC) isoform and (iii) the novel N-terminus truncated (PADI4-ΔN) isoform. The newly discovered isoform is not able to catalyze citrullination of vimentin (a well-characterized PADI4 target) and does not affect the enzymatic activity of the full-length isoform in in vitro competitive assays. These data suggest that allele variants (at the RA-associated SNP position) primarily alter the physiological ratio of the full-length and truncated PADI4 isoforms, which might lead to RA pathogenesis by an unknown mechanism.


Disclosure: D. M. Tóth, None; T. Ocskó, None; T. T. Glant, None; T. A. Rauch, None.

To cite this abstract in AMA style:

Tóth DM, Ocskó T, Glant TT, Rauch TA. Rheumatoid Arthritis-Associated Genetic Alteration Defines a New Promoter for Peptydil Arginine Deiminase 4 Gene [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/rheumatoid-arthritis-associated-genetic-alteration-defines-a-new-promoter-for-peptydil-arginine-deiminase-4-gene/. 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/rheumatoid-arthritis-associated-genetic-alteration-defines-a-new-promoter-for-peptydil-arginine-deiminase-4-gene/

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