Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.

Multiple different recombinant and peptide antigens are now available for serodiagnosis of Lyme disease (LD), but optimizing test utilization remains challenging. Since 1995 the Centers for Disease Control and Prevention (CDC) has recommended a 2-tiered serologic approach consisting of a first-tier...

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Autores principales:	Richard Porwancher, Lisa Landsberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75ac4a0f062f493f9a23a39e4c34413c
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spelling	oai:doaj.org-article:75ac4a0f062f493f9a23a39e4c34413c2021-12-02T20:08:25ZOptimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.1932-620310.1371/journal.pone.0253514https://doaj.org/article/75ac4a0f062f493f9a23a39e4c34413c2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253514https://doaj.org/toc/1932-6203Multiple different recombinant and peptide antigens are now available for serodiagnosis of Lyme disease (LD), but optimizing test utilization remains challenging. Since 1995 the Centers for Disease Control and Prevention (CDC) has recommended a 2-tiered serologic approach consisting of a first-tier whole-cell enzyme immunoassay (EIA) for polyvalent antibodies to Borrelia burgdorferi followed by confirmation of positive or equivocal results by IgG and IgM immunoblots [standard 2-tiered (STT) approach]. Newer modified 2-tiered (MTT) approaches employ a second-tier EIA to detect antibodies to B. burgdorferi rather than immunoblotting. We applied modern bioinformatic techniques to a large public database of recombinant and peptide antigen-based immunoassays to improve testing strategy. A retrospective CDC collection of 280 LD samples and 559 controls had been tested using the STT approach as well as kinetic-EIAs for VlsE1-IgG, C6-IgG, VlsE1-IgM, and pepC10-IgM antibodies. When used individually, the cutoff for each kinetic-EIA was set to generate 99% specificity. Utilizing logistic-likelihood regression analysis and receiver operating characteristic (ROC) techniques we determined that VlsE1-IgG, C6-IgG, and pepC10-IgM antibodies each contributed significant diagnostic information; a single-tier diagnostic score (DS) was generated for each sample using a weighted linear combination of antibody levels to these 3 antigens. DS performance was then compared to the STT and to MTT models employing different combinations of kinetic-EIAs. After setting the DS cutoff to match STT specificity (99%), the DS was 22.5% more sensitive than the STT for early-acute-phase disease (95% CI: 11.8% to 32.2%), 16.0% more sensitive for early-convalescent-phase disease (95% CI: 7.2% to 24.7%), and equivalent for detection of disseminated infection. The DS was also significantly more sensitive for early-acute-phase LD than MTT models whose specificity met or exceeded 99%. Prospective validation of this single-tier diagnostic score for Lyme disease will require larger studies using a broader range of potential cross-reacting conditions.Richard PorwancherLisa LandsbergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0253514 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Richard Porwancher Lisa Landsberg Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.
description	Multiple different recombinant and peptide antigens are now available for serodiagnosis of Lyme disease (LD), but optimizing test utilization remains challenging. Since 1995 the Centers for Disease Control and Prevention (CDC) has recommended a 2-tiered serologic approach consisting of a first-tier whole-cell enzyme immunoassay (EIA) for polyvalent antibodies to Borrelia burgdorferi followed by confirmation of positive or equivocal results by IgG and IgM immunoblots [standard 2-tiered (STT) approach]. Newer modified 2-tiered (MTT) approaches employ a second-tier EIA to detect antibodies to B. burgdorferi rather than immunoblotting. We applied modern bioinformatic techniques to a large public database of recombinant and peptide antigen-based immunoassays to improve testing strategy. A retrospective CDC collection of 280 LD samples and 559 controls had been tested using the STT approach as well as kinetic-EIAs for VlsE1-IgG, C6-IgG, VlsE1-IgM, and pepC10-IgM antibodies. When used individually, the cutoff for each kinetic-EIA was set to generate 99% specificity. Utilizing logistic-likelihood regression analysis and receiver operating characteristic (ROC) techniques we determined that VlsE1-IgG, C6-IgG, and pepC10-IgM antibodies each contributed significant diagnostic information; a single-tier diagnostic score (DS) was generated for each sample using a weighted linear combination of antibody levels to these 3 antigens. DS performance was then compared to the STT and to MTT models employing different combinations of kinetic-EIAs. After setting the DS cutoff to match STT specificity (99%), the DS was 22.5% more sensitive than the STT for early-acute-phase disease (95% CI: 11.8% to 32.2%), 16.0% more sensitive for early-convalescent-phase disease (95% CI: 7.2% to 24.7%), and equivalent for detection of disseminated infection. The DS was also significantly more sensitive for early-acute-phase LD than MTT models whose specificity met or exceeded 99%. Prospective validation of this single-tier diagnostic score for Lyme disease will require larger studies using a broader range of potential cross-reacting conditions.
format	article
author	Richard Porwancher Lisa Landsberg
author_facet	Richard Porwancher Lisa Landsberg
author_sort	Richard Porwancher
title	Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.
title_short	Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.
title_full	Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.
title_fullStr	Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.
title_full_unstemmed	Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.
title_sort	optimizing use of multi-antibody assays for lyme disease diagnosis: a bioinformatic approach.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/75ac4a0f062f493f9a23a39e4c34413c
work_keys_str_mv	AT richardporwancher optimizinguseofmultiantibodyassaysforlymediseasediagnosisabioinformaticapproach AT lisalandsberg optimizinguseofmultiantibodyassaysforlymediseasediagnosisabioinformaticapproach
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Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach.

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