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: 970

ACPA Activate Challenged Synovial Fibroblasts through a PAD Dependent Mechanism: A Potential Explanation of the “Second Hit Model” in RA

Meng Sun1, Vijay Joshua1, Akilan Krishnamurthy1, Aase Hensvold1, Yanying Liu2, Sergiu-Bogdan Catrina3, Caroline Ospelt4, Vivianne Malmström1, Johanna Steen1, Marianne Engström1, Heidi Wähämaa1, Bence Rethi1 and Anca I. Catrina1, 1Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 2Rheumatology Unit, Department of Medicine, Peking University People's Hospital, Beijing, China, 3Molecular Medicine and Surgery, Molecular Medicine and Surgery, Stockholm, Sweden, 4Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ACPA, Fibroblasts, interleukins (IL), rheumatoid arthritis (RA) and synovitis

  • 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: Monday, November 6, 2017

Title: Cytokines, Mediators, Cell-Cell Adhesion, Cell Trafficking and Angiogenesis Poster II: Mesenchymal Cells Do React - But How?

Session Type: ACR Poster Session B

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

Background/Purpose:

Anti-citrullinated proteins antibodies (ACPAs) injected in mice induce IL-8 dependent bone loss and arthralgia, but no synovial changes. We hypothesized that additional stimulus, sensitizing the synovial compartment to ACPA effects, is needed for the transition from bone to synovial pathology.

Methods:

Synovial biopsies were obtained from healthy volunteers and RA patients by arthroscopy. Synovial fibroblasts (SFs) were isolated from synovial tissue of RA patients by enzymatic digestion. Polyclonal ACPA and other non-ACPA IgGs were separated from peripheral blood of RA patients by affinity purification on a cyclic citrullinated peptide (CCP)-2 column. Monoclonal ACPAs were generated from synovial fluid single B-cells. SFs migration capacity was tested by scratch-assays in starved and non-starved cultures treated with ACPAs, with or without presence of IL-8. The results were evaluated by NIH ImageJ software. SF adhesion was analyzed by xCELLigence System Real-Time Cell Analyzer (ACEA bioscience). Peptidylarginine deiminases (PAD) expression and protein citrullination were evaluated by immunohistochemistry and immunofluorescence on SFs. Citrullination level of synovial biopsies were evaluated by biotinylated monoclonal ACPAs. The role of signaling pathways in the ACPA-mediated SF modulation was analyzed by using specific signal inhibitors and by monitoring protein phosphorylation using western blot.

Results:

Serum starvation of SFs increased citrullinated proteins and PAD expression. Starved but not non-starved SFs showed an increased mobility index following polyclonal ACPA stimulation to a mean±SD fold increase of 2.6±0.5. Similar effects were observed with monoclonal B09 but not C03, with a fold increase of the migration index of 1.8±0.4 for B09 antibody and 1.0±0.5 for C03 antibody. This effect was abolished by PAD inhibition as well as ACPA blocking with citrullinated but not native fibrinogen. Exogenous pro-inflammatory cytokines IL-8 and TNF induced PAD expression in SF and synergistically increased their mobility when added together with ACPA. Phosphorylation and inhibition studies of intracellular signaling pathways in starved SFs indicated an important role for PI3K-mediated signals in the ACPA-induced increase of SF mobility. Neither B09 nor C03 were binding to the non-inflammed healthy synovial tissues, while both B09 and C03 showed various degrees of binding to the inflammed RA synovial biopsies, with only B09 bidning the fibroblast cell population.

Conclusion:

We demonstrated that some but not all ACPAs fail to activate SFs in basal conditions but have a pronounce effect on cellular stressed SF. Our findings offer a novel scenario on how a synovial insult (in this case the in vitro induced cellular stress) that will normally resolve unobserved, might be essential for the transition towards chronic synovial changes in the presence of ACPA.


Disclosure: M. Sun, None; V. Joshua, None; A. Krishnamurthy, None; A. Hensvold, None; Y. Liu, None; S. B. Catrina, None; C. Ospelt, None; V. Malmström, None; J. Steen, None; M. Engström, None; H. Wähämaa, None; B. Rethi, None; A. I. Catrina, None.

To cite this abstract in AMA style:

Sun M, Joshua V, Krishnamurthy A, Hensvold A, Liu Y, Catrina SB, Ospelt C, Malmström V, Steen J, Engström M, Wähämaa H, Rethi B, Catrina AI. ACPA Activate Challenged Synovial Fibroblasts through a PAD Dependent Mechanism: A Potential Explanation of the “Second Hit Model” in RA [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/acpa-activate-challenged-synovial-fibroblasts-through-a-pad-dependent-mechanism-a-potential-explanation-of-the-second-hit-model-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 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/acpa-activate-challenged-synovial-fibroblasts-through-a-pad-dependent-mechanism-a-potential-explanation-of-the-second-hit-model-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