title: Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease.
abstract: The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease.
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Lauren J
authors.identifier: http://orcid.org/0000-0003-0026-6864
authors.initials: LJ
authors.lastname: Lahey
authors.affiliation: Division of Microbiology and Immunology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Panas
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Mao
authors.affiliation: Bio-Rad Laboratories, Hercules, California, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Delanoy
authors.affiliation: Bio-Rad Laboratories, Hercules, California, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Flanagan
authors.affiliation: Bio-Rad Laboratories, Hercules, California, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Binder
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Alison W
authors.initials: AW
authors.lastname: Rebman
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Montoya
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Soloski
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
authors.affiliation: Biopeptides Corp., East Setauket, New York, USA Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dattwyler
authors.affiliation: Biopeptides Corp., East Setauket, New York, USA Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Arnaboldi
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Aucott
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA wrobins@stanford.edu.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D015331:Cohort Studies; D003955:Diagnostic Tests, Routine / Q000379:methods*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008193:Lyme Disease / Q000175:diagnosis*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014481:United States; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins