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Diagnostic performance of the ZEUS Borrelia VlsE1/pepC10 assay in European LB patients: a case–control study

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European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

This retrospective case-control study assesses the sensitivity, specificity, and area under the curve of the ZEUS Borrelia VlsE1/pepC10 assay in comparison with the C6-ELISA in European patients with Lyme borreliosis, healthy blood donors, and potentially cross-reactive controls. We included a convenience series of 161 sera from patients with physician-confirmed early localized or disseminated Lyme borreliosis (n = 143), 400 sera from healthy blood donors and 44 sera with potentially cross-reactive antibodies, on which we performed the aforementioned serological assays and the recomLine immunoblot. Diagnostic parameters were compared in various single-tier and two-tier algorithms. The specificities of the C6-ELISA and the ZEUS Borrelia VlsE1/pepC10 were comparable in healthy blood donors (e.g., single-tier permissive: C6: 362/400, 90.5% [87.2–93.2]; VlsE1/pepC10: 361/400, 90.3% [86.9–93.0]). The C6-ELISA had an apparently higher sensitivity in EM sera (e.g., both time points combined: C6: 61/76, 80.3% [69.5–88.5]; VlsE1/pepC10: 54/76, 71.1% [59.5–80.9]), but these differences were all not-significant. Interestingly, the VlsE1/pepC10 assay had a significantly higher specificity in sera with potentially cross-reactive antibodies (e.g., single-tier permissive: C6: 34/44, 77.3% [62.2–88.5]; VlsE1/pepC10: 40/44, 90.9% [78.3–97.5]; p = 0.031). While the areas under the curve for both assays were excellent, that of the C6-ELISA exceeded that of the VlsE1/pepC10 (C6: AUC = 0.925; VlsE1/pepC10: AUC = 0.878; p = 0.003). The novel ZEUS Borrelia VlsE1/pepC10 assay has generally comparable diagnostic parameters to the C6-ELISA with potentially improved specificity in cross-reactive sera. Thus, it is a useful tool for the serodiagnosis of Lyme borreliosis in Europe.

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De-identified data for this project can be obtained from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the following colleagues for their assistance in performing and interpreting the immunoblots: Dieuwertje Hoornstra, MD; Nienke Verhaar, BSc; Jacqueline van Eck, BSc; and Alex Wagemakers, MD, PhD. They also thank Alexis Burnham, MSc, for her assistance in performing the ELISAs; Aradna Balak and Titia Moshe-Sterk for their assistance in selecting the healthy blood donors; Anneke Oei and Herman Kuiper, MD, for the inclusion of LB patients and development of the AMLC serum biobank; Jeroen Coumou, MD, PhD, for his assistance in providing an overview of the clinical information of the LB patients; Anita Buskermolen and other colleagues at the clinical serological laboratory of Amsterdam UMC for performing the C6-ELISAs and immunoblots for routine clinical diagnostics; and Alexander Platonov, PhD and Joris Koetsveld, MD, PhD for collecting and supplying the BMD sera.

Funding

The assays for this project were supplied free of charge by ITK Diagnostics (Uithoorn, The Netherlands) on behalf of ZEUS Scientific. Neither company had any role in the acquisition of the study data, analyses thereof or manuscript preparation. This study was supported by a grant to JWH and AV from the European Union through the European Regional Development Fund and the Interreg North Sea Region Programme 2014–2020 as part of the NorthTick project (reference number J-No: 38–2-7–19).

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Author notes

  1. M. E. Baarsma and A. Vrijlandt contributed equally to this work

Authors and Affiliations

  1. Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    M. E. Baarsma, A. Vrijlandt, J. Ursinus & J. W. Hovius

  2. Department of Blood‐borne Infections, Sanquin Research, Amsterdam, The Netherlands

    H. L. Zaaijer

  3. Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    S. Jurriaans & A. P. van Dam

Authors
  1. M. E. Baarsma
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  2. A. Vrijlandt
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  3. J. Ursinus
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  4. H. L. Zaaijer
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  5. S. Jurriaans
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  6. A. P. van Dam
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  7. J. W. Hovius
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Corresponding author

Correspondence to M. E. Baarsma.

Ethics declarations

Ethics approval

This project was submitted to the Medical Ethics Committee of Amsterdam UMC, which found it to be outside the scope of the Dutch Medical Research Involving Human Subjects Act (MEC decision W20_455).

Consent to participate

As this study used only de-identified leftover patient materials, informed consent from patients was not required. Healthy blood donors consented specifically to their materials being used for scientific purposes.

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Not applicable.

Conflict of interest

None of the authors have received any personal financial compensation from ZEUS Scientific or any of the other assays’ manufacturers. MEB and JWH have in the past collaborated with Bio-Rad Laboratories (Hercules, CA, USA), QIAGEN (Germantown, MD, USA), Oxford Immunotec (Oxford, UK), Invitalabs (Neuss, Germany) and AID (Strassberg, Germany) on unrelated projects on LB diagnostics. They have not received any personal financial compensation from any of the aforementioned companies. MEB, APvD and JWH collaborate with Pfizer (New York City, NY, USA) on unrelated projects on LD. They have not received any personal financial compensation from Pfizer or any of the other companies for these projects. The other authors report no potential conflicts of interest.

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Baarsma, M.E., Vrijlandt, A., Ursinus, J. et al. Diagnostic performance of the ZEUS Borrelia VlsE1/pepC10 assay in European LB patients: a case–control study. Eur J Clin Microbiol Infect Dis 41, 387–393 (2022). https://doi.org/10.1007/s10096-021-04372-6

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  • DOI: https://doi.org/10.1007/s10096-021-04372-6

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