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  • Review Article
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Lyme arthritis: linking infection, inflammation and autoimmunity

Nature Reviews Rheumatology volume 17, pages 449–461 (2021)Cite this article

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Abstract

Infectious agents can trigger autoimmune responses in a number of chronic inflammatory diseases. Lyme arthritis, which is caused by the tick-transmitted spirochaete Borrelia burgdorferi, is effectively treated in most patients with antibiotic therapy; however, in a subset of patients, arthritis can persist and worsen after the spirochaete has been killed (known as post-infectious Lyme arthritis). This Review details the current understanding of the pathogenetic events in Lyme arthritis, from initial infection in the skin, through infection of the joints, to post-infectious chronic inflammatory arthritis. The central feature of post-infectious Lyme arthritis is an excessive, dysregulated pro-inflammatory immune response during the infection phase that persists into the post-infectious period. This response is characterized by high amounts of IFNγ and inadequate amounts of the anti-inflammatory cytokine IL-10. The consequences of this dysregulated pro-inflammatory response in the synovium include impaired tissue repair, vascular damage, autoimmune and cytotoxic processes, and fibroblast proliferation and fibrosis. These synovial characteristics are similar to those in other chronic inflammatory arthritides, including rheumatoid arthritis. Thus, post-infectious Lyme arthritis provides a model for other chronic autoimmune or autoinflammatory arthritides in which complex immune responses can be triggered and shaped by an infectious agent in concert with host genetic factors.

Key points

  • A combination of spirochaetal and host genetic factors shape the outcome of Lyme arthritis, which ranges from mild, antibiotic-responsive joint inflammation to persistent, antibiotic-refractory autoinflammatory or autoimmune synovitis.

  • Certain highly inflammatory strains of Borrelia burgdorferi most commonly found in north-eastern USA are present at an increased frequency among patients who subsequently develop post-infectious Lyme arthritis.

  • The histology of post-infectious Lyme arthritis synovia is similar to that in other chronic inflammatory arthritides, such as rheumatoid arthritis, but there is greater microvascular damage in Lyme arthritis.

  • B. burgdorferi is no longer present in synovia after treatment with antibiotics, but B. burgdorferi peptidoglycan might persist and could be an important promoter of innate immune responses.

  • Dysregulated, excessive IFNγ responses and inadequate amounts of the anti-inflammatory cytokine IL-10 are a central feature of post-infectious Lyme arthritis, and contribute to persistent inflammation and the development of autoimmunity.

  • Synovial fibroblasts, the most common cell in the synovial lesion, become immune effector cells capable of altering the innate and adaptive immune microenvironment in Lyme arthritis.

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Fig. 1: Geographic distribution of Borrelia burgdorferi species relevant to human disease.
Fig. 2: Lyme arthritis stages and characteristics.
Fig. 3: Spirochaete invasion into joint tissue.
Fig. 4: Stages of arthritis and proposed tissue repair in antibiotic-responsive Lyme arthritis.
Fig. 5: Microvascular involvement in the synovial lesion of post-infectious Lyme arthritis.
Fig. 6: Cellular architecture of the post-infectious Lyme arthritis synovial lesion.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA

    Robert B. Lochhead

  2. Laboratory of Microbial Pathogenesis and Immunology, Division of Infectious Diseases, Wadsworth Center, Albany, NY, USA

    Klemen Strle

  3. Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    Sheila L. Arvikar & Allen C. Steere

  4. Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT, USA

    Janis J. Weis

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  5. Allen C. Steere
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R.B.L., K.S., J.J.W. and A.C.S. researched data for this article. All authors provided substantial contributions to discussion of content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Allen C. Steere.

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Lochhead, R.B., Strle, K., Arvikar, S.L. et al. Lyme arthritis: linking infection, inflammation and autoimmunity. Nat Rev Rheumatol 17, 449–461 (2021). https://doi.org/10.1038/s41584-021-00648-5

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