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Intrathecally produced IgG and IgM antibodies to recombinant VlsE, VlsE peptide, recombinant OspC and whole cell extracts in the diagnosis of Lyme neuroborreliosis

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Abstract

Detection of intrathecally produced specific antibodies (AI) is essential in the diagnosis of Lyme neuroborreliosis (LNB); however, the performance of various newer AI detection methods has not been systematically assessed. Here we assessed and compared advanced test systems for detecting borrelia IgG-AI and IgM-AI. Serum and cerebrospinal fluid (CSF) samples from well-defined LNB and tick-borne encephalitis (TBE) patients, 25 each, were tested with three antibody detection systems, one based on chemiluminescence (CLA) and two based on enzyme-linked immunosorbent assays (ELISA), employing different antigens for detection of IgG and IgM antibodies. In samples from patients with LNB, IgG-AI was detected in 20 samples by CLA, 19 by ELISA1, and 22 by ELISA2, and IgM-AI was detected in 16 samples by CLA, six by ELISA1, and 11 by ELISA2. In samples from TBE patients, IgG-AI was positive in one case by CLA and ELISA2, and in 7 cases by ELISA1, whereas IgM-AI was positive in one case by CLA and in none by ELISA. IgG-AI and IgM-AI were not detected within the first week of disease. Duration of disease correlated with IgG-AI while IgM-AI results were heterogeneous for each test assay. Moreover, the levels of IgG-AI, but not IgM-AI, correlated with protein concentration in CSF. IgG is the relevant immunoglobulin isotype for detecting intrathecal synthesis of borrelia antibodies. The highest sensitivity and specificity were achieved by the antibody detection assay using VlsE IR6 peptide. Detection of IgM-AI yielded heterogenous results and did not support the laboratory diagnosis of LNB.

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Acknowledgments

We are grateful to Brigitte Zinke for her excellent technical assistance. We thank the companies Diasorin Austria, Euroimmun Germany, and Medac Germany for donating the test kits for this study (LIAISON Borrelia IgG/IgMquant, Diasorin, Salugga, Italy, Lot Numbers: 089039/3 [IgG], 124023/1 [IgM]; Anti-Borrelia-plus-VlsE-ELISA [IgG], andAnti-Borrelia-ELISA [IgM], Euroimmun Medizinische Labordiagnostika AG, Lübeck, Germany, Lot Numbers: E110215AH [IgG], E110215AI [IgM]; and, Borrelia-IgG-/-IgM-ELISAmedac, Medac GmbH, Hamburg, Germany, Lot numbers: BORG05 [IgG], BORM04 [IgM]). FS received funding from Slovenian Research Agency (Grantp3-0296).

Conflict of interest

The authors FS, GS, and MM are members of the ESCMID study group on Lyme borreliosis, ESGBOR. The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute for Hygiene and Applied Immunology, Medical University of Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria

    Gerold Stanek & Mateusz Markowicz

  2. Medical Faculty, Institute for Biostatistics and Medical Informatics, University of Ljubljana, Ljubljana, Slovenia

    Lara Lusa

  3. Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

    Katarina Ogrinc & Franc Strle

Authors
  1. Gerold Stanek
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  2. Lara Lusa
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  3. Katarina Ogrinc
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  4. Mateusz Markowicz
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  5. Franc Strle
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Correspondence to Gerold Stanek or Franc Strle.

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Stanek, G., Lusa, L., Ogrinc, K. et al. Intrathecally produced IgG and IgM antibodies to recombinant VlsE, VlsE peptide, recombinant OspC and whole cell extracts in the diagnosis of Lyme neuroborreliosis. Med Microbiol Immunol 203, 125–132 (2014). https://doi.org/10.1007/s00430-013-0322-1

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  • DOI: https://doi.org/10.1007/s00430-013-0322-1

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