The development of an IgG avidity Western blot with potential to differentiate patients with active Lyme borreliosis from those with past infection

Sally Mavin (Corresponding Author), Roger Evans, Thomas Cornulier, Alan S Bowman

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Abstract

Objectives
Current serological methods cannot distinguish active from past infection with Borrelia burgdorferi sensu lato. The aim of this study was to develop an IgG avidity Western blot and assess its potential to differentiate patients with early and late Lyme borreliosis (LB) i.e. active disease, from those infected in the past.

Methods
An IgG avidity Western blot was developed. Penalized linear discriminant analysis (PLDA) was employed to compare the Western blot/avidity Western blot profiles of an evaluation panel consisting of 75 sera from patients with early (n = 26) and late (n = 24) LB and past infection (n = 25). The PLDA models produced were used to predict infection stage for 20 well characterised sera from the Centers for Disease Control and Prevention (CDC) Lyme disease serum repository and 112 routine seropositive sera (disease stage unknown), to validate and assess the usefulness of the avidity Western blot/avidity Western blot and PLDA approach.

Results
PLDA correctly classified 40/51 (78%) of patients when early LB and past infection groups in the evaluation panel were compared. Likewise, when late LB and past infection groups were compared, 34/49 (69%) were correct. The resultant PLDA models correctly predicted infection stage for 18/20 (90%) of the CDC sera, validating the use of the avidity Western blot/avidity Western blot and PLDA approach. When tested with the routine sera, 21/29 (72%) tested with the early LB vs. past infection model were correct but only 32/83 (39%) with the late LB vs. past infection model. Past infection was predicted for 40/112 (35%) of the routine sera, 80% of which correlated with the clinical picture.

Conclusion
The Western blot/avidity Western blot with PLDA approach shows exciting potential for being able to predict disease stage in some patients with LB, which could improve patient management.
Original languageEnglish
Pages (from-to)71-76
Number of pages6
JournalJournal of Microbiological Methods
Volume146
Early online date6 Feb 2018
DOIs
Publication statusPublished - Mar 2018

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Lyme Disease
Immunoglobulin G
Western Blotting
Discriminant Analysis
Infection
Serum
Centers for Disease Control and Prevention (U.S.)
Borrelia burgdorferi Group

Keywords

  • Borrelia burgdorferi
  • IgG avidity
  • laboratory diagnosis
  • lyme borreliosis
  • western blot

Cite this

@article{19f35874f2ed49e6882255b231669836,
title = "The development of an IgG avidity Western blot with potential to differentiate patients with active Lyme borreliosis from those with past infection",
abstract = "ObjectivesCurrent serological methods cannot distinguish active from past infection with Borrelia burgdorferi sensu lato. The aim of this study was to develop an IgG avidity Western blot and assess its potential to differentiate patients with early and late Lyme borreliosis (LB) i.e. active disease, from those infected in the past.MethodsAn IgG avidity Western blot was developed. Penalized linear discriminant analysis (PLDA) was employed to compare the Western blot/avidity Western blot profiles of an evaluation panel consisting of 75 sera from patients with early (n = 26) and late (n = 24) LB and past infection (n = 25). The PLDA models produced were used to predict infection stage for 20 well characterised sera from the Centers for Disease Control and Prevention (CDC) Lyme disease serum repository and 112 routine seropositive sera (disease stage unknown), to validate and assess the usefulness of the avidity Western blot/avidity Western blot and PLDA approach.ResultsPLDA correctly classified 40/51 (78{\%}) of patients when early LB and past infection groups in the evaluation panel were compared. Likewise, when late LB and past infection groups were compared, 34/49 (69{\%}) were correct. The resultant PLDA models correctly predicted infection stage for 18/20 (90{\%}) of the CDC sera, validating the use of the avidity Western blot/avidity Western blot and PLDA approach. When tested with the routine sera, 21/29 (72{\%}) tested with the early LB vs. past infection model were correct but only 32/83 (39{\%}) with the late LB vs. past infection model. Past infection was predicted for 40/112 (35{\%}) of the routine sera, 80{\%} of which correlated with the clinical picture.ConclusionThe Western blot/avidity Western blot with PLDA approach shows exciting potential for being able to predict disease stage in some patients with LB, which could improve patient management.",
keywords = "Borrelia burgdorferi, IgG avidity, laboratory diagnosis, lyme borreliosis, western blot",
author = "Sally Mavin and Roger Evans and Thomas Cornulier and Bowman, {Alan S}",
note = "We would like to thank all the users of the National Lyme Borreliosis Testing Laboratory for their help and support and Rachel Milner, Raigmore Hospital, Inverness, UK for her invaluable technical expertise. We would also like to thank Martin Schriefer and Claudia Mollins at CDC for providing their serum samples. Part of this research was funded by the Chief Scientist Office for Scotland (CZG/2/561). Preliminary results from this study were presented at the 14th International Conference on Lyme borreliosis and other tick-borne diseases ICLB, September 27-30, 2015, Vienna, Austria.",
year = "2018",
month = "3",
doi = "10.1016/j.mimet.2018.02.002",
language = "English",
volume = "146",
pages = "71--76",
journal = "Journal of Microbiological Methods",
issn = "0167-7012",
publisher = "Elsevier",

}

TY - JOUR

T1 - The development of an IgG avidity Western blot with potential to differentiate patients with active Lyme borreliosis from those with past infection

AU - Mavin, Sally

AU - Evans, Roger

AU - Cornulier, Thomas

AU - Bowman, Alan S

N1 - We would like to thank all the users of the National Lyme Borreliosis Testing Laboratory for their help and support and Rachel Milner, Raigmore Hospital, Inverness, UK for her invaluable technical expertise. We would also like to thank Martin Schriefer and Claudia Mollins at CDC for providing their serum samples. Part of this research was funded by the Chief Scientist Office for Scotland (CZG/2/561). Preliminary results from this study were presented at the 14th International Conference on Lyme borreliosis and other tick-borne diseases ICLB, September 27-30, 2015, Vienna, Austria.

PY - 2018/3

Y1 - 2018/3

N2 - ObjectivesCurrent serological methods cannot distinguish active from past infection with Borrelia burgdorferi sensu lato. The aim of this study was to develop an IgG avidity Western blot and assess its potential to differentiate patients with early and late Lyme borreliosis (LB) i.e. active disease, from those infected in the past.MethodsAn IgG avidity Western blot was developed. Penalized linear discriminant analysis (PLDA) was employed to compare the Western blot/avidity Western blot profiles of an evaluation panel consisting of 75 sera from patients with early (n = 26) and late (n = 24) LB and past infection (n = 25). The PLDA models produced were used to predict infection stage for 20 well characterised sera from the Centers for Disease Control and Prevention (CDC) Lyme disease serum repository and 112 routine seropositive sera (disease stage unknown), to validate and assess the usefulness of the avidity Western blot/avidity Western blot and PLDA approach.ResultsPLDA correctly classified 40/51 (78%) of patients when early LB and past infection groups in the evaluation panel were compared. Likewise, when late LB and past infection groups were compared, 34/49 (69%) were correct. The resultant PLDA models correctly predicted infection stage for 18/20 (90%) of the CDC sera, validating the use of the avidity Western blot/avidity Western blot and PLDA approach. When tested with the routine sera, 21/29 (72%) tested with the early LB vs. past infection model were correct but only 32/83 (39%) with the late LB vs. past infection model. Past infection was predicted for 40/112 (35%) of the routine sera, 80% of which correlated with the clinical picture.ConclusionThe Western blot/avidity Western blot with PLDA approach shows exciting potential for being able to predict disease stage in some patients with LB, which could improve patient management.

AB - ObjectivesCurrent serological methods cannot distinguish active from past infection with Borrelia burgdorferi sensu lato. The aim of this study was to develop an IgG avidity Western blot and assess its potential to differentiate patients with early and late Lyme borreliosis (LB) i.e. active disease, from those infected in the past.MethodsAn IgG avidity Western blot was developed. Penalized linear discriminant analysis (PLDA) was employed to compare the Western blot/avidity Western blot profiles of an evaluation panel consisting of 75 sera from patients with early (n = 26) and late (n = 24) LB and past infection (n = 25). The PLDA models produced were used to predict infection stage for 20 well characterised sera from the Centers for Disease Control and Prevention (CDC) Lyme disease serum repository and 112 routine seropositive sera (disease stage unknown), to validate and assess the usefulness of the avidity Western blot/avidity Western blot and PLDA approach.ResultsPLDA correctly classified 40/51 (78%) of patients when early LB and past infection groups in the evaluation panel were compared. Likewise, when late LB and past infection groups were compared, 34/49 (69%) were correct. The resultant PLDA models correctly predicted infection stage for 18/20 (90%) of the CDC sera, validating the use of the avidity Western blot/avidity Western blot and PLDA approach. When tested with the routine sera, 21/29 (72%) tested with the early LB vs. past infection model were correct but only 32/83 (39%) with the late LB vs. past infection model. Past infection was predicted for 40/112 (35%) of the routine sera, 80% of which correlated with the clinical picture.ConclusionThe Western blot/avidity Western blot with PLDA approach shows exciting potential for being able to predict disease stage in some patients with LB, which could improve patient management.

KW - Borrelia burgdorferi

KW - IgG avidity

KW - laboratory diagnosis

KW - lyme borreliosis

KW - western blot

U2 - 10.1016/j.mimet.2018.02.002

DO - 10.1016/j.mimet.2018.02.002

M3 - Article

VL - 146

SP - 71

EP - 76

JO - Journal of Microbiological Methods

JF - Journal of Microbiological Methods

SN - 0167-7012

ER -