Borrelia burgdorferipeptidoglycan is a persistent antigen in patients with Lyme arthritis

Abstract

Lyme disease is a multisystem disorder caused by the spirocheteBorrelia burgdorferi. A common late-stage complication of this disease is oligoarticular arthritis, often involving the knee. In ∼10% of cases, arthritis persists after appropriate antibiotic treatment, leading to a proliferative synovitis typical of chronic inflammatory arthritides. Here, we provide evidence that peptidoglycan (PG), a major component of theB. burgdorfericell envelope, may contribute to the development and persistence of Lyme arthritis (LA). We show thatB. burgdorferihas a chemically atypical PG (PGBb) that is not recycled during cell-wall turnover. Instead, this pathogen sheds PGBbfragments into its environment during growth. Patients with LA mount a specific immunoglobulin G response against PGBb, which is significantly higher in the synovial fluid than in the serum of the same patient. We also detect PGBbin 94% of synovial fluid samples (32 of 34) from patients with LA, many of whom had undergone oral and intravenous antibiotic treatment. These same synovial fluid samples contain proinflammatory cytokines, similar to those produced by human peripheral blood mononuclear cells stimulated with PGBb. In addition, systemic administration of PGBbin BALB/c mice elicits acute arthritis. Altogether, our study identifies PGBbas a likely contributor to inflammatory responses in LA. Persistence of this antigen in the joint may contribute to synovitis after antibiotics eradicate the pathogen. Furthermore, our finding thatB. burgdorferisheds immunogenic PGBbfragments during growth suggests a potential role for PGBbin the immunopathogenesis of other Lyme disease manifestations.