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: 0996

Bacteria-Derived Indole Drives Autoimmune Arthritis by Altering B Cell Glycosylation of Autoantibodies

Brandon Trent1, Meagan Chriswell2, Widian Jubair3 and Kristine Kuhn1, 1University of Colorado Anschutz Medical Campus, Aurora, CO, 2UC Denver SOM, Denver, CO, 3University of Colorado Denver, Denver, CO

Meeting: ACR Convergence 2020

Keywords: Autoantibody(ies), autoimmune diseases, B-Lymphocyte, metabolomics

  • Tweet
  • Email
  • Print
Session Information

Date: Sunday, November 8, 2020

Title: B Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session C

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

Background/Purpose: Background: Dysbiosis of gut bacterial communities in rheumatoid arthritis (RA) is a noted phenomenon in both murine models and human patients; however, the mechanisms from dysbiosis that promote RA pathogenesis remain unclear. Our lab previously demonstrated that administration of antibiotics to deplete the microbiota late in the course of murine collagen-induced arthritis (CIA) significantly ameliorated disease and correlated with changes in total antibody glycosylation patterns, known to occur in RA patients and affect complement fixation and FC receptor engagement. We hypothesized that the microbiota mediated antibody glycosylation via production of bacteria-specific metabolites.

Methods: Methods: CIA was induced by immunization of male 6-8 week-old DBA/1 mice with bovine type II collagen emulsified in complete Freund’s adjuvant on days 0 and 21. To understand the mechanisms by which late micriobiota depletion would significantly decrease CIA, we analyzed concentrations of cecal metabolites by LC-MS during CIA and after antibiotic treatment (1 mg/ml each ampicillin, neomycin, metronidazole and 0.5 mg/ml vancomycin). 10 mM indole or vehicle was then added to the drinking water containing antibiotics. Arthritis was evaluated based on a score of 0 (no swelling) to 4 (ankylosis) for each paw and summed for the mouse. Assessment of cell populations was performed by flow cytometry. Splenic B cells were evaluated ex vivo after stimulation with LPS (5μg/mL) and/or anti-IgM (10μg/mL) and total RNA was collected and analyzed via qRT-PCR.

Results: Results: Metabolomic profiling demonstrated a significant increase in bacteria-produced indole, a byproduct of tryptophan metabolism, in mice with CIA compared to unimmunized controls and those with CIA treated with antibiotics. Interestingly, administration of indole after antibiotic treatment resulted in a partial restoration of a CIA phenotype. Indole administration also resulted in increased T follicular helper cell (Tfh) and B cell populations in the Peyer’s patches and mesenteric lymph nodes in mice, but not the spleen. Furthermore, ex vivo stimulation of murine splenic B cells with indole induced gene expression of the B4Galt and Fut8 genes, transferases critical in antibody glycosylation.

Conclusion: Conclusions: Our results suggest that gut dysbiosis due to RA results in bacterial production of indole, which promotes RA pathogenesis via activation of B cell populations and altered antibody glycosylation patterns. Precise understanding of which indole metabolites are involved and how they engage cellular receptors will help elucidate the role of intestinal dysbiosis in RA development.


Disclosure: B. Trent, None; M. Chriswell, None; W. Jubair, None; K. Kuhn, None.

To cite this abstract in AMA style:

Trent B, Chriswell M, Jubair W, Kuhn K. Bacteria-Derived Indole Drives Autoimmune Arthritis by Altering B Cell Glycosylation of Autoantibodies [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/bacteria-derived-indole-drives-autoimmune-arthritis-by-altering-b-cell-glycosylation-of-autoantibodies-2/. Accessed .
  • Tweet
  • Email
  • Print

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/bacteria-derived-indole-drives-autoimmune-arthritis-by-altering-b-cell-glycosylation-of-autoantibodies-2/

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