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Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

Abstract
Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing.
AuthorsZachary P Weiner, Rebecca M Crew, Kevin S Brandt, Amy J Ullmann, Martin E Schriefer, Claudia R Molins, Robert D Gilmore
JournalClinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 22 Issue 11 Pg. 1176-86 (Nov 2015) ISSN: 1556-679X [Electronic] United States
PMID26376927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Immunoglobulin G
  • Immunoglobulin M
  • Recombinant Proteins
Topics
  • Antibodies, Bacterial (blood)
  • Antigens, Bacterial (immunology)
  • Bacterial Outer Membrane Proteins (immunology)
  • Borrelia burgdorferi (genetics, immunology)
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoblotting
  • Immunoglobulin G (blood)
  • Immunoglobulin M (blood)
  • Lyme Disease (diagnosis, microbiology)
  • Lyme Neuroborreliosis (diagnosis, immunology)
  • Myocarditis (immunology, microbiology)
  • Plasmids
  • Recombinant Proteins (immunology)
  • Serologic Tests
  • United States

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