Date: Sunday, October 21, 2018
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.
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.
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 10). https://acrabstracts.org/abstract/ifn-gamma-production-in-lyme-arthritis-synovial-tissue-promotes-differentiation-of-fibroblast-like-synoviocytes-into-inflammatory-effector-cells/. Accessed March 8, 2021.
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