Lyme arthritis: linking infection, inflammation and autoimmunity

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. Lyme arthritis, a manifestation of Lyme disease, can sometimes persist in a chronic post-infectious disease. In this Review, the authors argue that post-infectious Lyme arthritis could act as a model to improve understanding of other forms of chronic arthritis. 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 antibio