Lyme Arthritis Resolution with Antiserum to a 37-Kilodalton Borrelia burgdorferi Protein

摘要

A 37-kDa protein from Borrelia burgdorferi (the agent of Lyme disease) was identified as a target for immune-mediated resolution of Lyme arthritis. Studies in a mouse model have shown that arthritis resolution can be mediated by antibodies (against unknown target antigens) within immune sera from actively infected mice. Immune sera from infected mice were therefore used to screen a B. burgdorferi genomic expression library. A gene was identified whose native product is a putative lipoprotein of approximately 37 kDa, referred to here as arthritis-related protein (Arp). Active and passive immunization of mice with recombinant Arp or Arp antiserum, respectively, did not protect mice from challenge inoculation. However, when Arp antiserum was administered to severe combined immunodeficient (SCID) mice with established infections and with ongoing arthritis and carditis, treatment selectively induced arthritis resolution without affecting the status of carditis or influencing the status of infection, including spirochetemia. The selective arthritis-resolving effect of Arp antiserum mimics the activity of immune serum from immunocompetent mice when such serum is transferred into SCID mice with established infections. The arp gene could not be amplified from unrelated B. burgdorferi isolates but hybridized with those isolates only under very-low-stringency conditions. Arp antiserum reacted against proteins of similar size in a wide range of B. burgdorferi isolates.