ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 987

Anti-citrullinated Protein Antibodies Induce Subclinical Inflammation, Bone Loss and Pain in Mice

Akilan Krishnamurthy1, Yogan Kisten 2, Alexandra Circiumaru 3, Katalin Sandor 4, Koji Sakurabas 5, Gustaf Wigerblad 6, Peter Damberg 7, Heidi Wähämaa 3, Patrik Jarvolli 7, Vivianne Malmström 8, Lars Klareskog 9, Camilla I Svensson 10, Juan Jimenez Jimenez Andrade 11, Bence Rethi 3 and Anca Catrina 9, 1Rheumatology unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Solna, Stockholm, 2Rheumatology unit Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, Stockholm, Stockholms Lan, Sweden, 3Rheumatology unit Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, Stockholm, 4Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden, stockholm, Sweden, 5Rheumatology unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Solna, stockholm, Sweden, 6karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, 7Karolinska Institutet, Karolinska Experimental Research and Imaging Centre (KERIC), stockholm, Sweden, stockholm, Sweden, 8Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Institutet, Stockholm, Sweden., Stockholm, Sweden, 9Rheumatology unit Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden, 10Karolinska Institutet, Physiology and Pharmacology, stockholm, Sweden, Stockholm, Sweden, 11Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, Mexico, Tamaulipas, Mexico

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: anti-citrullinated protein/peptide antibodies (ACPA), Autoimmunity, Bone and inflammation, Magnetic resonance imaging (MRI)

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Monday, November 11, 2019

Session Title: RA – Animal Models Poster

Session Type: Poster Session (Monday)

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

Background/Purpose: Autoantibodies against citrullinated proteins (ACPAs) could be associated with bone loss, pain and tenosynovitis prior to disease onset in human rheumatoid arthritis (RA) and induce bone loss and pain when injected in mice. We aimed to investigate if transfer of human ACPAs into mice could induce tenosynovitis and/or subclinical inflammation.

Methods: Monoclonal ACPA (1325:04C03 and 1325:01B09) and control (1362:01E02) antibodies (mAbs) were generated from synovial plasma or memory B cells of RA patients. 2mg of combination of monoclonal ACPAs or control antibody were injected in BALB/c female mice (12-16 Weeks). Pain-like behavior was monitored by measuring mechanical hypersensitivity using von Frey filaments every 3 days and estimation by up-down Dixon method. Bone mineral density was measured by micro-CT. Using specially designed mobilization casts, dedicated mouse MRI coils, and gadolinium enhanced contrast medium, the hind limbs of these mice were scanned and evaluated for any signs of soft tissue joint inflammation. The MRI images were scored for the presence of synovial thickening, effusion and tendon inflammatory changes by 3 readers in a blinded manner.

Results: ACPAs (1325:04C03 and 1325:01B09) induced significantly more pronounced pain-like behavior (lasting for at least 4 weeks) and reduction of the trabecular bone thickness in the hind limbs, whereas no such effect was seen with the control monclonals generated in the same way as the monoclonal ACPAs. While no macroscopic sign of joint inflammation could be detected, MRI data shows sub-clinical joint inflammatory changes (such as perfusion of contrast in tendons, soft tissues and joints) in mice injected with ACPAs but not in those injected with control mAb. Using a semiquantitative score for the degree of inflammatory changes (0- Within normal range, 1-Mild, 2- Moderate and 3- Severe) we were able to show that ACPA induced mild to moderate inflammatory changes affecting tendon thickness, joint effusion and soft tissue enhancements, in contrast to control antibody or Saline injected mice which was within normal range (figure 1 below).

Conclusion: We show that ACPA induces pain-like behavior, bone loss and sub-clinical inflammation in mice, a model that mimics the pre-clinical state of ACPA positive RA

Figure 1. Representative MRI image showing the ACPA induced sub-clinical changes in the joints of the mice


Disclosure: A. Krishnamurthy, None; Y. Kisten, None; A. Circiumaru, None; K. Sandor, None; K. Sakurabas, None; G. Wigerblad, None; P. Damberg, None; H. Wähämaa, None; P. Jarvolli, None; V. Malmström, None; L. Klareskog, BMS, 2, Janssen, 2, Pfizer, 2; C. Svensson, None; J. Jimenez Andrade, None; B. Rethi, None; A. Catrina, None.

To cite this abstract in AMA style:

Krishnamurthy A, Kisten Y, Circiumaru A, Sandor K, Sakurabas K, Wigerblad G, Damberg P, Wähämaa H, Jarvolli P, Malmström V, Klareskog L, Svensson C, Jimenez Andrade J, Rethi B, Catrina A. Anti-citrullinated Protein Antibodies Induce Subclinical Inflammation, Bone Loss and Pain in Mice [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/anti-citrullinated-protein-antibodies-induce-subclinical-inflammation-bone-loss-and-pain-in-mice/. Accessed February 25, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-citrullinated-protein-antibodies-induce-subclinical-inflammation-bone-loss-and-pain-in-mice/

Advanced Search

Your Favorites

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

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.