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: 2714

The Paracaspase MALT1 Plays a Central Role in the Pathogenesis of Rheumatoid Arthritis

Elisabeth Gilis1, Jens Staal2, Rudi Beyaert2 and Dirk Elewaut3, 1Molecular Immunology and Inflammation Unit, VIB Inflammation Research Center, Ghent, Belgium, Gent, Belgium, 2Molecular Immunology and Inflammation Unit, VIB Inflammation Research Center, Ghent, Belgium, 3VIB Inflammation Research Center, University of Ghent, Ghent, Belgium

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: antigen-presenting cells and rheumatoid arthritis (RA), T cells

  • Tweet
  • Email
  • Print
Session Information

Date: Tuesday, November 7, 2017

Title: T Cell Biology and Targets in Autoimmune Disease Poster II

Session Type: ACR Poster Session C

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

Background/Purpose: One of the hallmarks of many inflammatory arthritides is their strong linkage with MHC-signalling, which is mirrored by the marked role for adaptive immunity. Accordingly, rheumatoid arthritis (RA) is characterized by the activation of auto-reactive T-cells and the development of auto-antibodies. T-cells may additionally respond to non-TCR mediated signals, which are essential in driving their effector functions. Pathways leading to the modulation of both innate and adaptive signals are therefore of marked interest to study in arthritic diseases. The paracaspase MALT1 is a key player in the activation and proliferation of immune and non-immune cells. These cells include the lymphoid, myeloid and mast cells, indicating MALT1’s crucial role in both innate and adaptive signaling. Therefore, MALT1 is regarded a promising target for the treatment of autoimmune diseases and defining its role in the pathogenesis of inflammatory arthritis is a critical first step.

Methods: To unravel MALT1’s role in inflammatory arthritis, we initially assessed MALT1-activation in mice that were challenged with collagen-induced arthritis (CIA), the prototype model for antigen-induced RA. We then addressed the role of MALT1 in the pathogenesis of inflammatory arthritis by challenging MALT1-deficient mice to distinct models of arthritis (CIA and CAIA). Additionally, CIA was induced in CD4-specific MALT1-deficient mice to determine the importance of MALT1 in T-cells. Bone homeostasis was assessed by micro-CT analysis, a 3 point bending test to test bone strength and by osteoclastogenesis assays using RANKL induced osteoclastogenesis and resorption pit assays. Immunophenotyping of T cell and regulatory T cell subsets was conducted in spleen and lymph nodes and anti-collagen II specific antibody development was measured by ELISA.

Results: We provide evidence that MALT1 plays a crucial role in the pathogenesis of RA as MALT1-deficent mice were completely protected against CIA. This complete protection was additionally observed in CD4-specific MALT1-deficient mice, indicating that the selective ablation of MALT1 in CD4-positive cells is sufficient for the observed resistance against CIA. This was reflected by markedly lower induction of anti-collagen type II antibodies. CAIA on the other hand, which is a T- and B-cell independent model of RA, did not depend on the presence of MALT1, since both MALT1+/+ and MALT1-/- mice showed comparable symptoms of RA. MALT1 deficient mice show an osteoporotic phenotype but osteoclastogenesis was normal suggesting an indirect effect. MALT1 deficient mice lack natural Tregs which could account for the osteoporotic phenotype. Accordingly, CD4-specific MALT1-deficient mice also had an osteoporotic phenotype on microCT with impaired bone strength.

Conclusion: Overall, our data highlight that MALT1 plays a crucial role in the pathogenesis of inflammatory arthritis but has a dual role on inflammation versus bone homeostasis. Our data indicate an osteoporotic phenotype in the absence of MALT1 caused by lack of Tregs.


Disclosure: E. Gilis, None; J. Staal, None; R. Beyaert, None; D. Elewaut, Scientific Research Flanders; Research Council Ghent University; Interuniversity Attraction Pole., 2,Boehringer Ingelheim; Pfizer; UCB; Merck; Novartis; Janssen; Abbvie, 5.

To cite this abstract in AMA style:

Gilis E, Staal J, Beyaert R, Elewaut D. The Paracaspase MALT1 Plays a Central Role in the Pathogenesis of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-paracaspase-malt1-plays-a-central-role-in-the-pathogenesis-of-rheumatoid-arthritis/. Accessed .
  • Tweet
  • Email
  • Print

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-paracaspase-malt1-plays-a-central-role-in-the-pathogenesis-of-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