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Abstract Number: 951

IFN-Gamma Production in Lyme Arthritis Synovial Tissue Promotes Differentiation of Fibroblast-like Synoviocytes into Inflammatory Effector Cells

Robert Lochhead1, David Ordonez-Del Valle1, Sheila Arvikar2, Allen C. Steere2 and Klemen Strle3, 1Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, BOSTON, MA, 2Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 3Department of Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, BOSTON, MA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Arthritis, Fibroblasts, interferons and synovial cells, Lyme disease, synovial fluid

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Session Information

Date: Sunday, October 21, 2018

Session Title: 3S104 ACR Abstract: Infection-Related Rheumatic Disease (946–951)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Lyme arthritis (LA), a late-disease manifestation of Borrelia burgdorferi infection, usually responds to antibiotic therapy. However, some patients may develop a proliferative synovitis lasting months to several years after spirochetal killing, called post-infectious LA. Their synovial lesion is associated with robust expression of interferon (IFN)-responsive genes and suppressed expression of genes associated wound healing. However, it is not yet clear which cell populations contribute to these LA-associated gene signatures.

Methods: Hematopoietic and stromal cell populations in the post-infectious LA synovial lesion were analyzed at the cellular level by flow cytometric analysis and immunofluorescence microscopy. Observations in human patients were validated in vitro using primary human fibroblast-like synoviocytes (FLS) derived from post-infectious LA synovial tissue, and ex vivo using murine LA models.

Results: T cells and NK cells were highly abundant in synovial tissue and were IFNγ-positive by intracellular cytokine staining. HLA-DR+ FLS were present throughout the synovial lesion, particularly in areas of inflammation. Primary human FLS stimulated with IFNγ expressed HLA-DR molecules and a large number of genes associated with autoimmune/autoinflammatory inflammatory responses, similar to ex vivo findings. Co-stimulation of FLS with B. burgdorferi and IFNγ potentiated a significantly greater inflammatory cytokine and chemokine response than either B. burgdorferi or IFNγ stimulation alone. Tissue from joints of B. burgdorferi­­-infected C57BL/6 mice, which develop mildly inflammatory LA, had a wound-healing myofibroblast phenotype, whereas tissue from severely arthritogenic C3H/HeN and Il10-/- (B6) mice had a pro-inflammatory phenotype, dominated by excessive IFN responses, similar to human findings.

Conclusion:

These results suggest that post-infectious LA may be initiated during infection if accompanied by dysregulated IFNγ responses. Under these conditions, B. burgdorferi infection may lead to differentiation of FLS into a highly inflammatory phenotype that may persist if IFNγ-producing lymphocytes are chronically activated within the synovial lesion after the infection is cleared, resulting in excessive inflammation and tissue damage.


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

To cite this abstract in AMA style:

Lochhead R, Ordonez-Del Valle D, Arvikar S, Steere AC, Strle K. IFN-Gamma Production in Lyme Arthritis Synovial Tissue Promotes Differentiation of Fibroblast-like Synoviocytes into Inflammatory Effector Cells [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/ifn-gamma-production-in-lyme-arthritis-synovial-tissue-promotes-differentiation-of-fibroblast-like-synoviocytes-into-inflammatory-effector-cells/. Accessed February 2, 2023.
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