1887

Abstract

A multiplex-bead-based assay for the detection of serum antibodies to was evaluated. The assay contained 13 different antigens in both the IgG and the IgM assay; thus, a total of 26 measurement results were available from each sample. A total of 49 Danish patients with Lyme neuroborreliosis (LNB), 218 Danish blood donor controls, a set of 61 Swedish patients with LNB and 139 Swedish non-LNB patients investigated for suspected LNB were used. There are four parts developed in this study: a characterization of the sero-epidemiological antibody-response pattern, the construction of a diagnostic score, evaluation of the scoring method using an independent dataset and an assessment of the analytical quality of the multiplex assay. The VlsE IgG had the highest diagnostic value with an AUC (area under the curve) of 96% on the receiver operating characteristic curve. The OspC IgM had AUCs just above 80%. All the other antigens had both low quantitative reactivity and lower contrast in the patients with LNB compared to controls. The diagnostic value of the assay may be improved by using a logistic model giving a sensitivity of 90 and 79% for the specificities at 92 and 98%, respectively. Overall, the patients with LNB had serum reactivity in IgG VlsE, but modest antibody reactivity in the remaining 12 IgG and 13 IgM antibody measurements. Using a logistic regression model with five IgG and two IgM antigens, the sensitivity and specificity of the assay was improved; but the IgG VlsE component alone contributed most of the diagnostic contrast.

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2015-03-01
2024-04-19
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References

  1. Aguero-Rosenfeld M. E. 2008; Lyme disease: laboratory issues. Infect Dis Clin North Am 22:301–313 [View Article][PubMed]
    [Google Scholar]
  2. Aguero-Rosenfeld M. E., Wang G., Schwartz I., Wormser G. P. 2005; Diagnosis of Lyme borreliosis. Clin Microbiol Rev 18:484–509 [View Article][PubMed]
    [Google Scholar]
  3. CDC 1995; Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep 44:590–591[PubMed]
    [Google Scholar]
  4. Dessau R. B. 2013; Diagnostic accuracy and comparison of two assays for Borrelia-specific IgG and IgM antibodies: proposals for statistical evaluation methods, cut-off values and standardization. J Med Microbiol 62:1835–1844 [View Article][PubMed]
    [Google Scholar]
  5. Dessau R. B., Bangsborg J. M., Ejlertsen T., Skarphedinsson S., Schønheyder H. C. 2010a; Utilization of serology for the diagnosis of suspected Lyme borreliosis in Denmark: survey of patients seen in general practice. BMC Infect Dis 10:317 [View Article][PubMed]
    [Google Scholar]
  6. Dessau R. B., Ejlertsen T., Hilden J. 2010b; Simultaneous use of serum IgG and IgM for risk scoring of suspected early Lyme borreliosis: graphical and bivariate analyses. APMIS 118:313–323 [View Article][PubMed]
    [Google Scholar]
  7. Dessau R. B., Eliasson I., Skarpaas T., Nyman D. 2011; Report from a survey of laboratory methods used in Scandinavia. Testing for Lyme borreliosis in the Nordic countries – variations in strategies and rate of seropositivity http://dskm.dk/Serological-20testing-20for-20Lyme.pdf
    [Google Scholar]
  8. Hauser U., Lehnert G., Lobentanzer R., Wilske B. 1997; Interpretation criteria for standardized Western blots for three European species of Borrelia burgdorferi sensu lato. J Clin Microbiol 35:1433–1444[PubMed]
    [Google Scholar]
  9. Hauser U., Lehnert G., Wilske B. 1999; Validity of interpretation criteria for standardized Western blots (immunoblots) for serodiagnosis of Lyme borreliosis based on sera collected throughout Europe. J Clin Microbiol 37:2241–2247[PubMed]
    [Google Scholar]
  10. Henningsson A. J., Tjernberg I., Malmvall B. E., Forsberg P., Ernerudh J. 2011; Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study. J Neuroinflammation 8:36 [View Article][PubMed]
    [Google Scholar]
  11. Henningsson A. J., Christiansson M., Tjernberg I., Löfgren S., Matussek A. 2014; Laboratory diagnosis of Lyme neuroborreliosis: a comparison of three CSF anti-Borrelia antibody assays. Eur J Clin Microbiol Infect Dis 33:797–803 [View Article][PubMed]
    [Google Scholar]
  12. Hunfeld K. P., Kraiczy P. 2009; When is the best time to order a Western blot and how should it be interpreted?. Curr Probl Dermatol 37:167–177 [View Article][PubMed]
    [Google Scholar]
  13. Hunfeld K. P., Stanek G., Straube E., Hagedorn H. J., Schörner C., Mühlschlegel F., Brade V. 2002; Quality of Lyme disease serology. Lessons from the German proficiency testing program 1999–2001. A preliminary report. Wien Klin Wochenschr 114:591–600[PubMed]
    [Google Scholar]
  14. Müller I., Freitag M. H., Poggensee G., Scharnetzky E., Straube E., Schoerner Ch., Hlobil H., Hagedorn H.-J., Stanek G. et al. 2012; Evaluating frequency, diagnostic quality, and cost of Lyme borreliosis testing in Germany: a retrospective model analysis. Clin Dev Immunol 2012:595427 [View Article][PubMed]
    [Google Scholar]
  15. Mygland Å., Ljøstad U., Fingerle V., Rupprecht T., Schmutzhard E., Steiner I. 2010; EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 17:8–16 [View Article][PubMed]
    [Google Scholar]
  16. Pepe M. S. 2003; Combining multiple test results. In The Statistical Evaluation of Medical Tests for Classification and Prediction pp. 267–276 Oxford: Oxford University Press;
    [Google Scholar]
  17. R Core Team 2013 R: a Language and Environment for Statistical Computing Vienna: R Foundation for Statistical Computing;
    [Google Scholar]
  18. Robertson J., Guy E., Andrews N., Wilske B., Anda P., Granström M., Hauser U., Moosmann Y., Sambri V. et al. 2000; A European multicenter study of immunoblotting in serodiagnosis of Lyme borreliosis. J Clin Microbiol 38:2097–2102[PubMed]
    [Google Scholar]
  19. Stanek G., Reiter M. 2011; The expanding Lyme Borrelia complex – clinical significance of genomic species?. Clin Microbiol Infect 17:487–493 [View Article][PubMed]
    [Google Scholar]
  20. Stanek G., Fingerle V., Hunfeld K. P., Jaulhac B., Kaiser R., Krause A., Kristoferitsch W., O’Connell S., Ornstein K. et al. 2011; Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect 17:69–79 [View Article][PubMed]
    [Google Scholar]
  21. Stanek G., Wormser G. P., Gray J., Strle F. 2012; Lyme borreliosis. Lancet 379:461–473 [View Article][PubMed]
    [Google Scholar]
  22. Tjernberg I., Henningsson A. J., Eliasson I., Forsberg P., Ernerudh J. 2011; Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis. J Infect 62:149–158 [View Article][PubMed]
    [Google Scholar]
  23. Wilske B., Hauser U., Lehnert G., Jauris-Heipke S. 1998; Genospecies and their influence on immunoblot results. Wien Klin Wochenschr 110:882–885[PubMed]
    [Google Scholar]
  24. Wilske B., Zöller L., Brade V., Eiffert H., Göbel U. B., Stanek G., Pfister H. W. 2000; MIQ12, Lyme-borreliose. In Qualitätsstandards in der Mikrobiologisch-Infektiologischen Diagnostik pp. 1–59 Edited by Mauch H., Lütticken R. Munich: Urban & Fischer Verlag;
    [Google Scholar]
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