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Borrelia burgdorferi VlsE antigen for the serological diagnosis of Lyme borreliosis

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Abstract

In this study, raising and development of antibody response to Borrelia burgdorferi infection in 66 Italian patients suffering from culture-confirmed Lyme borreliosis erythema migrans (EM) was investigated. Sixty-two of 66 cultures obtained from biopsies were identified as B. afzelii by PCR. A total of 175 serially collected serum samples were tested by using two different sets of commercial assays: Enzygnost Lyme link VlsE/IgG and Enzygnost Borreliosis IgM (DADE Behring, Marburg, Germany) and LIAISON Borrelia IgG and IgM (Diasorin, Saluggia, Italy). Considering only samples obtained at first presentation when EM was clinically evident, 49/66 patients (72.4%) were IgG or IgM positive by Enzygnost, whereas 33/66 (50.0%) patients were IgG or IgM positive by LIAISON. Taking into account the follow-up period, eight patients sero-converted for IgG or IgM by Enzygnost and four by LIAISON. Similar and very good specificity values were obtained by all methods. Testing sera obtained from blood donors (n = 300) and from patients suffering from some of the most common biological conditions possibly resulting in false-positive reactivity in Lyme disease serology (n = 100) showed that Enzygnost Lyme link VlsE/IgG was the more specific (98.3%), followed by LIAISON Borrelia IgG (96.5%), and considering IgM tests, Enzygnost Borreliosis IgM showed to be 95.3%% specific, whereas the LIAISON Borrelia IgM was 92.8% specific. Recombinant VlsE antigens obtained from all three B.burgdorferi genospecies pathogenic to humans (included in Enzygnost Lyme link VlsE/IgG) greatly improved serodiagnosis of Lyme disease.

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References

  1. Gern L, Estrada-Pena A, Frandsen F, Gray JS, Jaenson TG, Jongejan F, Kahl O, Korenberg E, Mehl R, Nuttall PA (1998) European reservoir hosts of Borrelia burgdorferi sensu lato. Zentralbl Bakteriol 287:196–204

    PubMed  CAS  Google Scholar 

  2. Steere AC (2001) Lyme disease. N Engl J Med 345:115–125

    Article  PubMed  CAS  Google Scholar 

  3. Steere AC, Broderick TF, Malawista SE (1978) Erythema chronicum migrans and Lyme arthritis: epidemiologic evidence for a tick vector. Am J Epidemiol 108:312–321

    PubMed  CAS  Google Scholar 

  4. Weber K, Pfister HW (1993) History of Lyme borreliosis in Europe. In: Weber K, Burgdorfer W (eds) Aspects of Lyme borreliosis. Springer, Berlin, Heidelberg, New York, pp 1–20

    Google Scholar 

  5. Baranton G, Postic D, Saint Girons I, Boerlin P, Piffaretti JC, Assous M, Grimont PAD (1992) Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol 42:378–383

    Article  PubMed  CAS  Google Scholar 

  6. Stanek G, Strle F (2003) Lyme borreliosis. Lancet 362:1639–1647

    Article  PubMed  Google Scholar 

  7. Wang G, van Dam AP, Schwartz I, Dankert J (1999) Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin Microbiol Rev 12:633–653

    PubMed  CAS  Google Scholar 

  8. Wilske B, Busch U, Eiffert H, Fingerle V, Pfister HW, Rössler D, Preac-Mursic V (1996) Diversity of OspA and OspC among cerebrospinal fluid isolates of Borrelia burgdorferi sensu lato from patients with neuroborreliosis in Germany. Med Microbiol Immunol 184:195–201

    Article  PubMed  CAS  Google Scholar 

  9. Mathiesen DA, Oliver JH Jr, Kolbert CP, Tullson ED, Johnson BJ, Campbell GL, Mitchell PD, Reed KD, Telford SR III, Anderson JF, Lane RS, Persing DH (1997) Genetic heterogeneity of Borrelia burgdorferi in the United States. J Infect Dis 175:98–107

    PubMed  CAS  Google Scholar 

  10. Nadelman RB, Wormser GP (1998) Lyme borreliosis. Lancet 352:557–565

    Article  PubMed  CAS  Google Scholar 

  11. Saint Girons I, Gern L, Gray JS, Guy EC, Korenberg E, Nuttall PA, Rijpkema SG, Schonberg A, Stanek G, Postic D (1998) Identification of Borrelia burgdorferi sensu lato species in Europe. Zentralbl Bakteriol 287:190–195

    PubMed  CAS  Google Scholar 

  12. Wormser GP (2006) Early Lyme disease. N Engl J Med 354:2794–2801

    Article  PubMed  CAS  Google Scholar 

  13. Gilmore RD Jr, Mbow ML, Stevenson B (2001) Analysis of Borrelia burgdorferi gene expression during life cycle phases of the tick vector Ixodes scapularis. Microbes Infect 3:799–808

    Article  PubMed  CAS  Google Scholar 

  14. Schwan TG, Piesman J, Golde WT, Dolan MC, Rosa PA (1995) Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci USA 92:2909–2913

    Article  PubMed  CAS  Google Scholar 

  15. Das S, Barthold SW, Giles SS, Montgomery RR, Telford SR III, Fikrig E, Persing DH (1997) Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. J Clin Investig 99:987–995

    Article  PubMed  CAS  Google Scholar 

  16. Fikrig E, Barthold SW, Sun W, Feng W, Telford SR III, Flavell RA (1997) Borrelia burgdorferi P35 and P37 proteins, expressed in vivo, elicit protective immunity. Immunity 6:531–539

    Article  PubMed  CAS  Google Scholar 

  17. Gilmore RD Jr, Mbow ML, Stevenson B (2001) Analysis of Borrelia burgdorferi gene expression during life cycle phases of the tick vector Ixodes scapularis. Microbes Infect 3:799–808

    Article  PubMed  CAS  Google Scholar 

  18. Hauser U, Krahl H, Peters H, Fingerle V, Wilske B (1998) Impact of strain heterogeneity on Lyme disease serology in Europe: comparison of enzyme-linked immunosorbent assays using different species of Borrelia burgdorferi sensu lato. J Clin Microbiol 36:427–436

    PubMed  CAS  Google Scholar 

  19. 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  CAS  Google Scholar 

  20. Heikkila T, Seppala I, Saxen H, Panelius J, Yrjanainen H, Lahdenne P (2002) Species-specific serodiagnosis of Lyme arthritis and neuroborreliosis due to Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii by using decorin binding protein A. J Clin Microbiol 40:453–460

    Article  PubMed  CAS  Google Scholar 

  21. Robertson J, Guy E, Andrews N, Wilske B, Anda P, Granström M, Hauser U, Moosmann Y, Sambri V, Schellekens J, Stanek G, Gray J (2000) European multicenter study of immunoblotting in serodiagnosis of Lyme borreliosis. J Clin Microbiol 38:2097–2102

    PubMed  CAS  Google Scholar 

  22. Centers for Disease Control and Prevention (1995) Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. Morb Mortal Wkly Rep 44:590–591

    Google Scholar 

  23. Wilske B, Zöller L, Brade V, Eiffert M, Göbel UB, Stanek G, Pfister HW (2000). MIQ 12 Lyme-Borreliose. In: Mauch H, Lütticken R (eds) Qualitätsstandards in der mikrobiologisch-infektiologischen Diagnostik. Urban and Fischer, Munich, pp 1–59

    Google Scholar 

  24. Bacon RM, Biggerstaff BJ, Schriefer M, Gilmore RD, Philipp MT, Steere A, Wormser GP, Marques AR, Johnson BJB (2003) Improved serodiagnosis of Lyme disease by kinetic EIAs using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with two-tiered testing. J Infect Dis 187:1187–1199

    Article  PubMed  CAS  Google Scholar 

  25. Zhang JR, Hardham JM, Barbour AG, Norris SJ (1997) Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89:275–285

    Article  PubMed  CAS  Google Scholar 

  26. Marangoni A, Sparacino M, Cavrini F, Storni E, Mondardini V, Sambri V, Cevenini R (2005) Comparative evaluation of three different EIA methods for the diagnosis of early culture-confirmed Lyme disease in Italy. J Med Microbiol 54:361–367

    Article  PubMed  CAS  Google Scholar 

  27. Cinco M, Murgia R (2006) Evaluation of the C6 enzyme-linked immunoadsorbent assay for the serodiagnosis of Lyme borreliosis in north-eastern Italy. New Microbiol 29:139–141

    PubMed  CAS  Google Scholar 

  28. Göttner G, Schulte-Spechtel U, Wilske B (2004) Heterogeneity of the immunodominant surface protein VlsE among the three genospecies of Borrelia burgdorferi pathogenic for humans. Int J Med Microbiol 293(suppl 37):172–173

    PubMed  Google Scholar 

  29. Marangoni A, Sambri V, Cimmino C, Caruso G, Mondardini V, Cevenini R (1999) Evaluation of the immune response in culture-confirmed Lyme Borreliosis Erythema migrans patients. Zentralbl Bakteriol 289:736–739

    Google Scholar 

  30. Marangoni A, Sambri V, Accardo S, Cavrini F, Mondardini V, Moroni A, Storni E, Cevenini R (2006) A decrease of the IgG antibody response against VlsE protein of Borrelia burgdorferi s.l. correlates with the resolution of clinical signs in antibiotic treated early Lyme disease patients. Clin Vaccine Immunol 13:525–529

    Article  PubMed  CAS  Google Scholar 

  31. Marconi RT, Garon CF (1992) Development of chain reaction primers sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J Clin Microbiol 30:2830–2834

    PubMed  CAS  Google Scholar 

  32. Picken RN (1992) Polymerase chain reaction primers and probes derived from flagellin gene sequences for specific detection of the agents of Lyme disease and North American relapsing fever. J Clin Microbiol 30:99–114

    PubMed  CAS  Google Scholar 

  33. Cadenas FM, Rais O, Jouda F, Douet V, Humair PF, Moret J, Gern L (2007) Phenology of Ixodes ricinus and infection with Borrelia burgdorferi sensu lato along a north-and south-facing altitudinal gradient on Chaumont Mountain, Switzerland. J Med Entomol 44:683–693

    Article  PubMed  Google Scholar 

  34. Stünzner D, Hubalek Z, Halouzka J, Postic D, Pierer K, Marth E (1998) Prevalence of Borrelia burgdorferi s.l. in Ixodes ricinus ticks from Styria (Austria) and species identification by PCR-RFLP analysis. Zentralbl Bakteriol 288:471–478

    PubMed  Google Scholar 

  35. Stünzner D, Pierer K, Hubalek Z, Halouzka J, Aberer E, Millner MM, Marth E (1999) Species identification of Borrelia burgdorferi sensu lato from tick and human isolates in Styria (Austria) by PCR-RFLP analysis. Wien Klin Wochenschr 111:994–996

    PubMed  Google Scholar 

  36. Lebech AM (2002) Polymerase chain reaction in diagnosis of Borrelia burgdorferi infections and studies on taxonomic classification. APMIS Suppl 105:1–40

    PubMed  Google Scholar 

  37. Liang FT, Steere AC, Marques AR, Johnson BJB, Miller JN, Philipp MT (1999) Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi VlsE. J Clin Microbiol 37:3990–3996

    PubMed  CAS  Google Scholar 

  38. Philipp MT, Bowers LC, Fawcett PT, Jacobs MB, Liang FT, Marques AR, Mitchell PD, Purcell JE, Ratterree MS, Straubinger RK (2001) Antibody response to IR6, a conserved immunodominant region of the VlsE lipoprotein, wanes rapidly after antibiotic treatment of Borrelia burgdorferi infection in experimental animals and in humans. J Infect Dis 84:870–878

    Article  Google Scholar 

  39. Philipp MT, Marques AR, Fawcett PT, Dally LG, Martin DS (2003) C6 test as an indicator of therapy outcome for patients with localized or disseminated Lyme borreliosis. J Clin Microbiol 41:4955–4960

    Article  PubMed  Google Scholar 

  40. Philipp MT, Wormser G, Marques AD, Bittker S, Martin DS, Nowakowski J, Dally LG (2005) A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin Diagn Lab Immunol 12:1069–1074

    Article  PubMed  CAS  Google Scholar 

  41. Smismans A, Goossens VJ, Nulens E, Bruggeman CA (2006) Comparison of five different immunoassays for the detection of Borrelia burgdorferi IgM and IgG antibodies. Clin Microbiol Infect 12:648–655

    Article  PubMed  CAS  Google Scholar 

  42. Embers ME, Wormser GP, Schwartz I, Martin DS, Philipp MT (2007) Borrelia burgdorferi spirochetes that harbor only a portion of the lp28-1 plasmid elicit antibody responses that are detectable with the C6 Lyme test. Clin Vaccine Immunol 14:90–93

    Article  PubMed  CAS  Google Scholar 

  43. Marangoni A, Sparacino M, Mondardini V, Cavrini F, Storni E, Donati M, Cevenini R, Sambri V (2005) Comparative evaluation of two enzyme linked immunosorbent assay methods and three Western Blot methods for the diagnosis of culture-confirmed early Lyme Borreliosis in Italy. New Microbiol 28:37–43

    PubMed  CAS  Google Scholar 

  44. Aguero-Rosenfeld ME, Nowakowski J, Bittker S, Cooper D, Nadelman RB, Wormser GP (1996) Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans. J Clin Microbiol 34:1–9

    PubMed  CAS  Google Scholar 

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Acknowledgements

We are extremely grateful to Dr. Valeria Mondardini, Division of Infectious Diseases, Ospedale di Belluno, Belluno, Italy for providing specimens from Lyme disease patients.

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  1. Section of Microbiology, DMCSS–University of Bologna, St.Orsola Hospital, via Massarenti 9, 40138, Bologna, Italy

    A. Marangoni, A. Moroni, S. Accardo & R. Cevenini

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  1. A. Marangoni
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  2. A. Moroni
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  3. S. Accardo
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  4. R. Cevenini
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Correspondence to A. Marangoni.

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Marangoni, A., Moroni, A., Accardo, S. et al. Borrelia burgdorferi VlsE antigen for the serological diagnosis of Lyme borreliosis. Eur J Clin Microbiol Infect Dis 27, 349–354 (2008). https://doi.org/10.1007/s10096-007-0445-7

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