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Abstract Number: 1020

The Inflammatory and Proliferative Synovial Lesion in Post-Infectious Lyme Arthritis Results from Impaired Wound Healing

Robert Lochhead1,2, David Ordonez-Del Valle1,2, Klemen Strle2,3, Sheila Arvikar1,2, John Aversa4 and Allen Steere1,2, 1Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA, 2Department of Medicine, Harvard Medical School, BOSTON, MA, 3Department of Immunology and Inflammatory Diseases, Massachusetts General Hospital, BOSTON, MA, 4School of Medicine, Yale University, New Haven, CT

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Arthritis, Lyme disease, osteoarthritis and rheumatoid arthritis (RA), Synovial Immune Biology

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Session Information

Date: Monday, November 6, 2017

Session Title: Genetics, Genomics and Proteomics Poster II

Session Type: ACR Poster Session B

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

Background/Purpose: Lyme arthritis (LA) is initially triggered by Borrelia burgdorferi infection, but in some patients, the synovitis persists despite 2-3 months of antibiotic therapy and spirochetal killing, called post-infectious LA. As in rheumatoid arthritis (RA), post-infectious LA is characterized by autoimmune inflammation and synovial hyperplasia. Our recent microRNA analysis revealed that antibacterial responses characterized the infectious phase of LA, and impaired wound healing may contribute to inflammatory and proliferative synovitis following resolution of infection. In mice, impaired wound repair and elevated interferon (IFN) responses during B. burgdorferiinfection are associated with severe murine LA, but the role of impaired wound healing has not been explored in post-infectious LA or RA.

Methods: High-throughput RNA sequencing was performed using synovial tissue from patients with post-infectious LA (n=14), RA (n=5), and osteoarthritis (OA, n=5), and analyzed using in-house and online bioinformatics tools. Cells expressing IFNγ were identified by intracellular cytokine staining and flow cytometry of cells collected from fresh synovial tissue and synovial fluid. Immunofluorescent (IF) microscopy was used to identify IFNγ-responsive cells from patient synovial biopsies.

Results: 1001 genes were differentially expressed (DE) in post-infectious LA synovial tissue compared with OA tissue, of which 517 (43%) were interferon-regulated genes. In addition, 85/190 (45%) of genes in the response to wounding gene ontology (GO) set were DE in post-infectious LA patients compared with OA patients. Of these, ~1/3 were involved in coagulation, cell proliferation/differentiation, and extracellular matrix (ECM) formation, and were down-regulated in post-infectious LA, but less consistently in RA, compared with OA; whereas ~2/3 were involved in immune activation, IFN responses, and ECM degradation, and were up-regulated in both post-infectious LA and RA, compared with OA. Cytotoxic CD8+ T cells were a major source IFNγ in post-infectious LA and RA synovial tissue, and fibroblasts within foci of active synovitis expressed high levels of IFNγ-inducible HLA-DR molecules.

Conclusion: These data show that impaired wound healing is a previously unrecognized component of the inflammatory-proliferative synovial pathology of post-infectious LA and RA. We propose that dysregulated wound healing in inflamed tissue may potentiate break in immune tolerance during the early stages of autoimmune development. Thus, post-infectious LA provides a natural human model of infection-induced autoimmunity, in which impaired wound healing leads to autoimmune synovial pathology of the chronic inflammatory arthritides, including RA.


Disclosure: R. Lochhead, None; D. Ordonez-Del Valle, None; K. Strle, None; S. Arvikar, None; J. Aversa, None; A. Steere, None.

To cite this abstract in AMA style:

Lochhead R, Ordonez-Del Valle D, Strle K, Arvikar S, Aversa J, Steere A. The Inflammatory and Proliferative Synovial Lesion in Post-Infectious Lyme Arthritis Results from Impaired Wound Healing [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-inflammatory-and-proliferative-synovial-lesion-in-post-infectious-lyme-arthritis-results-from-impaired-wound-healing/. Accessed March 1, 2021.
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