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Abstract Number: 2437

Translocation of Intestinal Bacteria to Axial and Peripheral Joints in a Model of Spondyloarthropathy

Benjamin Cai1, Rabina Giri2, Helen Benham3, Linda Rehaume1, Geoffery Strutton3, Anne-Sophie Bergot1 and Ranjeny Thomas4, 1Frazer Institute, The University of Queensland, Woolloongabba, Australia, 2Mater Research Institute-UQ, Woolloongabba, Australia, 3Princess Alexandra Hospital, Woolloongabba, Australia, 4Frazer Institute, The University of Queensland, Brisbane, Australia

Meeting: ACR Convergence 2023

Keywords: Animal Model, Ankylosing spondylitis (AS), Inflammation, microbiome, spondyloarthritis

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Session Information

Date: Tuesday, November 14, 2023

Title: Abstracts: Spondyloarthritis Including Psoriatic Arthritis – Basic Science

Session Type: Abstract Session

Session Time: 2:00PM-3:30PM

Background/Purpose: In spondylarthropathy (SpA), such as psoriatic arthritis (PsA) and ankylosing spondylitis (AS), arthritis is often associated with gut inflammation. After systemic β-1,3-glucan (curdlan) injection, ZAP70W163C SKG mice develop IL23-dependent SpA-like spondylarthritis, ileitis and faecal dysbiosis with enrichment in Gram-negative pathobionts over commensals, recapitulating human SpA disease spectrum. Spondylitis in AS patients does not respond to anti-IL-23. To assess the interaction of intestinal dysbiosis and spondyloarthritis, we treated diseased SKG mice with anti-IL-23p19.

Methods: Specific-pathogen-free SKG or BALB/c control mice were injected i.p. with curdlan followed by anti-IL-23p19 antibody or isotype three weeks later. At eight weeks, ileum, ankle and sacroiliac joints were collected, paraffin-embedded for histology and scored for arthritis and ileitis. Tissue sections were analysed by fluorescence imaging using universal bacterial DNA EUB338 and non-sense EUB338 control probes, combined with anti-MPO or anti-IBA-1 antibodies for neutrophils and macrophages.

Results: At 8 weeks post-curdlan, isotype-treated SPF SKG mice developed ileitis, enthesitis, axial and peripheral arthritis while anti-IL-23p19-treated SKG mice had much less severe disease, and BALB/c mice remained healthy. In inflamed ileum of isotype-treated SKG mice, EUB338+ bacteria translocated from the lumen to the gut lamina propria, where they colocalised with infiltrating MPO+ neutrophils and IBA-1+ resident macrophages. In arthritic axial and ankle joints, EUB338+ bacterial DNA was detected in the blood vessels, tendon entheses, ligaments and the bone marrow, associated with bone and cartilage destruction. MPO+ neutrophils and IBA-1+ resident macrophages infiltrated the areas of inflammation. In anti-IL-23p19-treated SKG mice, bacterial signals were detected in entheses but not the bone marrow. No bacterial signal was detected in BALB/c tissues.

Conclusion: In SKG mice, curdlan triggers IL-23-dependent gut permeability and ileitis that allows mucosal invasion of bacteria, and dissemination of intestinal bacterial DNA to axial and peripheral joints’ bone marrow and entheses through the vasculature, similar to reactive arthritis. While anti-IL-23 blocks bone marrow entry of bacterial DNA, it fails to limit the entheseal spread after disease onset. This suggests a potential mechanism by which inflammation is perpetuated in ankylosing spondylitis.


Disclosures: B. Cai: None; R. Giri: None; H. Benham: None; L. Rehaume: None; G. Strutton: None; A. Bergot: None; R. Thomas: CSL, 2, 5, Janssen-Cilag, 6, Sandoz, 6.

To cite this abstract in AMA style:

Cai B, Giri R, Benham H, Rehaume L, Strutton G, Bergot A, Thomas R. Translocation of Intestinal Bacteria to Axial and Peripheral Joints in a Model of Spondyloarthropathy [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/translocation-of-intestinal-bacteria-to-axial-and-peripheral-joints-in-a-model-of-spondyloarthropathy/. Accessed .
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