Immunopathogenesis Of Human Inflammatory Arthritis: Lessons From Lyme And Reactive Arthritis

Abstract

Human inflammatory arthritic diseases developing in response to infections with known pathogens provide unique models for studying the molecular and cellular mechanisms underlying human chronic inflammatory diseases. For example, Lyme disease serves as an appropriate clinical entity for immunopathogenetic studies, since the tickborne spirochete Borrelia burgdorferi, which causes Lyme disease, has been identified [1]. Patients with Lyme disease frequently develop intermittent inflammatory symptoms [2]. In both adults [2] and children [3], most Lyme disease patients will have resolution of their arthritic symptoms over time. However, a subset of patients with Lyme disease (~10*) develop a chronic inflammatory arthritis that resembles other forms of human inflammatory arthritis, including rheumatoid arthritis [4]. Synovial tissue obtained from this subset of patients is histopathologically identical to that of rheumatoid arthritis [2]. T lymphocytes, predominantly CD4~h T cells, are present in the synovial tissue in both arthritides [5]. Similarly, reactive arthritis triggered by Yersinia enterocolitica provides another clinical model for studying the pathogenesis of human inflammatory arthritis. Among the bacteria known to cause reactive arthritis, which include Salmonella, Shigella, Campylobacter, and Chlamydia species, Yersinia is one of the more common etiologic genera [6]. Y. enterocolitica causes acute gastroenteritis. At 1-3 weeks after infection, a subset of patients develop a reactive arthritis that varies from mild arthralgia to severe polyarthritis and usually resolves within a few weeks or months in most patients. Synovial fluid and blood samples from these patients are particularly valuable for pathogenetic studies, since they can be obtained at an early stage of disease from patients with characteristic clinical features, a known time of disease onset, and a serologically and microbiologically confirmed diagnosis. As in Lyme arthritis, a subset of these patients (10*) will