We showed thatArthritis is a frequent and major complication of natural and experimental infection with Borrelia burgdorferi (1,5,30,34). Moreover, arthritis is induced following vaccination, with (14, 25) or without (28) challenge with B. burgdorferi. The immunologic events responsible for these B. burgdorferi-associated arthritides are poorly understood. We demonstrated that induction of chronic severe destructive arthritis following vaccination and challenge was dependent on B. burgdorferi-specific T lymphocytes (23). Treatment of vaccinated animals with anti-CD4 antibody prevented the development of severe destructive arthritis when the animals were challenged with the Lyme spirochete (24). Activated or primed CD4 ϩ T cells participated in the development of arthritis that included cartilage and bone erosion (24).Recently, we also showed that B. burgdorferi-vaccinated interferon gamma-deficient (IFN-␥ 0 ) mice challenged with B. burgdorferi developed a prominent chronic severe destructive osteoarthropathy (12). These results along with those of Brown and Reiner (6) present compelling evidence that interferon gamma (IFN-␥) does not play a major role in the induction or propagation of arthritis in the infection (6) or vaccinationchallenge (12) model of B. burgdorferi-associated arthritis. This suggests that other cytokines, chemokines, or other immune regulators are responsible for the induction of arthritis.
CD4؉ CD25 Our investigators showed previously that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-␥°) mice challenged with B. burgdorferi developed a prominent chronic destructive osteoarthropathy (13). The tibiotarsal joint of vaccinated and challenged mice displayed chronic hypertrophy and hyperplasia characterized by erosion of articular cartilage and focal destruction of bone. Treatment of vaccinated IFN-␥°m ice with anti-interleukin-17 (IL-17) antibody followed by challenge with B.
An in vitro assay was used to characterize the borreliacidal activity of sera from Lyme disease patients. The mean percentage of killing was 23% with sera from patients with a single erythema migrans lesion, 42% from patients with multiple lesions, 58% from patients with Lyme arthritis of short duration, and 83% from patients with Lyme arthritis of long duration. Borreliacidal activity was abrogated when Lyme disease serum was treated with anti-human IgM or IgG1. In addition, human sera from Lyme arthritis patients containing borreliacidal antibody prevented the induction of Lyme arthritis in irradiated hamsters challenged with the Lyme spirochete. Removal of outer surface protein A antibodies from late Lyme disease sera caused reductions in the borreliacidal antibody titer. The results demonstrate an important role for borreliacidal antibody against infection with B. burgdorferi in humans and confirm that detection of borreliacidal antibody in human sera can be a specific serodiagnostic test for Lyme disease.
Early Lyme borreliosis sera with significant titers of anti-outer surface protein C (OspC) borreliacidal antibodies were identified. Human anti-OspC borreliacidal antibodies could be either IgM or IgG. Significant concentrations of borreliacidal activity were detected after vaccination of mice with OspC. Detection of anti-OspC borreliacidal activity was dependent on surface expression of OspC by Borrelia burgdorferi isolate 50772. The ability of OspC to induce borreliacidal antibodies in vivo and after vaccination offers another possible explanation for the ability of vaccination with OspC to protect against infection with B. burgdorferi. Furthermore, detection of anti-OspC borreliacidal antibodies, especially IgM antibodies, in early Lyme borreliosis sera provides additional evidence that borreliacidal antibody detection may be useful for the serodiagnosis of early Lyme borreliosis.
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