Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease

ABSTRACT BBK32 is a multifunctional surface lipoprotein expressed by Borrelia burgdorferi sensu lato, the causative agent of Lyme disease. Previous studies suggested that BBK32 could be a sensitive antigen target of new, more effective, serodiagnostic assays for the laboratory diagnosis of Lyme dise...

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Autores principales:	Christina Toumanios, Lauren Prisco, Raymond J. Dattwyler, Paul M. Arnaboldi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	BBK32 Borrelia burgdorferi Lyme disease serology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e1d3068e8ba641199823c0099c9522ee
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spelling	oai:doaj.org-article:e1d3068e8ba641199823c0099c9522ee2021-11-15T15:22:20ZLinear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease10.1128/mSphere.00111-192379-5042https://doaj.org/article/e1d3068e8ba641199823c0099c9522ee2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00111-19https://doaj.org/toc/2379-5042ABSTRACT BBK32 is a multifunctional surface lipoprotein expressed by Borrelia burgdorferi sensu lato, the causative agent of Lyme disease. Previous studies suggested that BBK32 could be a sensitive antigen target of new, more effective, serodiagnostic assays for the laboratory diagnosis of Lyme disease. However, nonspecific antibody binding to full-length BBK32 has hampered its use as a target in clinical assays. Specificity can be improved by the use of peptides composed of linear B cell epitopes that are unique to B. burgdorferi, eliminating cross-reactive epitopes that bind to antibodies generated by non-B. burgdorferi antigens. In this study, we identified linear B cell epitopes in 2 regions, BBK32 amino acids 16 to 30 [BBK32(16–30)] and BBK32 amino acids 51 to 80 [BBK32(51–80)], by probing overlapping peptide libraries of BBK32 with serum from patients with early Lyme disease. We screened synthetic peptides containing these epitopes using a large panel of serum (n = 355) obtained from patients with erythema migrans lesions (early Lyme disease), Lyme arthritis, syphilis, rheumatoid arthritis, or healthy volunteers. BBK32(16–30) demonstrated a nearly universal antibody binding in serum from all patients, indicating that regions of BBK32 are highly cross-reactive. BBK32(51–80) was less cross-reactive, being able to distinguish serum from Lyme disease patients from control patient serum; however, an unacceptable level of antibody binding was still observed in control samples, resulting in a reduced specificity (94.7%). These results indicate that BBK32 contains cross-reactive epitopes that make it a poor antigen target for inclusion in a serodiagnostic assay for Lyme disease and highlight the difficulties in identifying highly sensitive and specific seroassay targets. IMPORTANCE Lyme disease is an infectious disease that has the potential to cause significant morbidity with damage to nervous and musculoskeletal systems if left untreated. Appropriate antibiotic treatment during early infection prevents disease progression. Unfortunately, currently available diagnostics are suboptimal in the detection of early disease. The inability to confirm Borrelia infection using laboratory methods during early disease is, in part, responsible for much of the controversy surrounding Lyme disease today. As a result, there has been significant investment in the identification of new antigen targets to generate diagnostic assays that are more sensitive for the detection of early infection. The importance of our research is that in our evaluation of BBK32, an antigen that was previously identified as a promising target for use in serodiagnostics, we found a high degree of cross-reactivity that could compromise the specificity of assays that utilize this antigen, leading to false-positive diagnoses.Christina ToumaniosLauren PriscoRaymond J. DattwylerPaul M. ArnaboldiAmerican Society for MicrobiologyarticleBBK32Borrelia burgdorferiLyme diseaseserologyMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	BBK32 Borrelia burgdorferi Lyme disease serology Microbiology QR1-502
spellingShingle	BBK32 Borrelia burgdorferi Lyme disease serology Microbiology QR1-502 Christina Toumanios Lauren Prisco Raymond J. Dattwyler Paul M. Arnaboldi Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease
description	ABSTRACT BBK32 is a multifunctional surface lipoprotein expressed by Borrelia burgdorferi sensu lato, the causative agent of Lyme disease. Previous studies suggested that BBK32 could be a sensitive antigen target of new, more effective, serodiagnostic assays for the laboratory diagnosis of Lyme disease. However, nonspecific antibody binding to full-length BBK32 has hampered its use as a target in clinical assays. Specificity can be improved by the use of peptides composed of linear B cell epitopes that are unique to B. burgdorferi, eliminating cross-reactive epitopes that bind to antibodies generated by non-B. burgdorferi antigens. In this study, we identified linear B cell epitopes in 2 regions, BBK32 amino acids 16 to 30 [BBK32(16–30)] and BBK32 amino acids 51 to 80 [BBK32(51–80)], by probing overlapping peptide libraries of BBK32 with serum from patients with early Lyme disease. We screened synthetic peptides containing these epitopes using a large panel of serum (n = 355) obtained from patients with erythema migrans lesions (early Lyme disease), Lyme arthritis, syphilis, rheumatoid arthritis, or healthy volunteers. BBK32(16–30) demonstrated a nearly universal antibody binding in serum from all patients, indicating that regions of BBK32 are highly cross-reactive. BBK32(51–80) was less cross-reactive, being able to distinguish serum from Lyme disease patients from control patient serum; however, an unacceptable level of antibody binding was still observed in control samples, resulting in a reduced specificity (94.7%). These results indicate that BBK32 contains cross-reactive epitopes that make it a poor antigen target for inclusion in a serodiagnostic assay for Lyme disease and highlight the difficulties in identifying highly sensitive and specific seroassay targets. IMPORTANCE Lyme disease is an infectious disease that has the potential to cause significant morbidity with damage to nervous and musculoskeletal systems if left untreated. Appropriate antibiotic treatment during early infection prevents disease progression. Unfortunately, currently available diagnostics are suboptimal in the detection of early disease. The inability to confirm Borrelia infection using laboratory methods during early disease is, in part, responsible for much of the controversy surrounding Lyme disease today. As a result, there has been significant investment in the identification of new antigen targets to generate diagnostic assays that are more sensitive for the detection of early infection. The importance of our research is that in our evaluation of BBK32, an antigen that was previously identified as a promising target for use in serodiagnostics, we found a high degree of cross-reactivity that could compromise the specificity of assays that utilize this antigen, leading to false-positive diagnoses.
format	article
author	Christina Toumanios Lauren Prisco Raymond J. Dattwyler Paul M. Arnaboldi
author_facet	Christina Toumanios Lauren Prisco Raymond J. Dattwyler Paul M. Arnaboldi
author_sort	Christina Toumanios
title	Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease
title_short	Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease
title_full	Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease
title_fullStr	Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease
title_full_unstemmed	Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease
title_sort	linear b cell epitopes derived from the multifunctional surface lipoprotein bbk32 as targets for the serodiagnosis of lyme disease
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e1d3068e8ba641199823c0099c9522ee
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Linear B Cell Epitopes Derived from the Multifunctional Surface Lipoprotein BBK32 as Targets for the Serodiagnosis of Lyme Disease

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