title: Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease.
abstract: Most immunogenic proteins of Borrelia burgdorferi, the causative agent of Lyme disease, are known or expected to contain multiple B cell epitopes. However, the kinetics of the development of human B cell responses toward the various epitopes of individual proteins during the course of Lyme disease has not been examined. Using the highly immunogenic VlsE as a model Ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of early to late manifestations of Lyme disease. The results demonstrate the existence of asynchronous, independently developing, Ab responses against the two major immunogenic regions of the VlsE molecule in the human host. Despite their strong immunogenicity, the target epitopes were inaccessible to Abs on intact spirochetes, suggesting a lack of direct immunoprotective effect. These observations document the association of immune reactivity toward specific VlsE sequences with different phases of Lyme disease, demonstrating the potential use of detailed epitope mapping of Ags for staging of the infection, and offer insights regarding the pathogen's possible immune evasion mechanisms.
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY 10032;
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Jacek
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY 10032;
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Tang
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, D-23560 Lubeck, Germany;
authors.forename: Lars
authors.identifier: http://orcid.org/0000-0003-4698-3316
authors.initials: L
authors.lastname: Komorowski
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY 10032;
authors.forename: Mary
authors.initials: M
authors.lastname: Ajamian
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, D-23560 Lubeck, Germany;
authors.forename: Christian
authors.identifier: http://orcid.org/0000-0002-0286-8482
authors.initials: C
authors.lastname: Probst
authors.affiliation: University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Brian
authors.identifier: http://orcid.org/0000-0002-2406-4776
authors.initials: B
authors.lastname: Stevenson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY 10595; and.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Wormser
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814.
authors.forename: Adriana R
authors.identifier: http://orcid.org/0000-0002-5403-4551
authors.initials: AR
authors.lastname: Marques
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY 10032; aa819@columbia.edu.
authors.forename: Armin
authors.identifier: http://orcid.org/0000-0002-5776-8585
authors.initials: A
authors.lastname: Alaedini
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D015151:Immunoblotting; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D008074:Lipoproteins; C105546:VlsE protein, Borrelia burgdorferi