Research Article
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Testing for Lyme borreliosis: could serology tell more?

Year 2020, Volume: 5 Issue: 3, 85 - 93, 30.09.2020

Abstract

Purpose:
Remnant antibodies might be prevalent in the general population, thus recognizing relevant seropositivity might be challenging. The sequential nature of the anti-Borrelia antibody response might be diagnostically utilized. We aimed to specify details which might potentially be useful in orientating the diagnostic schedule.

Methods:
We processed the sera of 1304 patients using a recombinant antigen-based ELISA between Aprils of 2017 and 2019. Seroreactivity (when coherent with the anamnestic data) was confirmed with a line immunoassay (LIA). ELISA testing (IgG and/or IgM) was reactive in 539 cases. 107 patients with persistent symptoms tested positive or borderline with IgG ELISA.

Results:
A significant difference was observed (Mann-Whitney U-test p=0.003) between the LIA scores of patients with characteristic (arthritis, acrodermatitis, neuropathy, other objective neurologic disorder; n=83; median LIA score: 16) and non-specific symptoms (entirely subjective complaints, other known disease, lone subfebrility, uveitis; n=24; median LIA score: 6). 101 of the 107 patients tested positive for IgG against any specific protein by LIA. Those with a LIA score reaching the group median of 15 (n=51) displayed strong anti-VlsE IgG positivity or a typical late IgG antibody (against p100, p18 or p39) more often than those below (88,2% vs. 30% and 100% vs. 38% respectively, Χ2 p<0.0001).

Conclusions:
Weak LIA positivity (especially anti-VlsE IgG) in combination with the lack of late antibodies in patients with persistent symptoms might suggest the presence of remnant antibodies and prompt scrupulous differential diagnosis.

Supporting Institution

South-Pest Central Hospital, National Institute for Infectology and Haematology, Budapest, Hungary

Project Number

EB/14/2019 (license number by Institutional Commitee of Science and Research Ethics)

References

  • Eldin C, Raffetin A, Bouiller K, Hansmann Y, Roblot F, Raoult D, et al. Review of European and American guidelines for the diagnosis of Lyme borreliosis. Médecine Mal. Infect. 2019 1;49:121–32. doi: 10.1016/j.medmal.2018.11.011
  • Two-step Laboratory Testing Process | Lyme Disease | CDC [Internet]. 2018 21 [cited 2019 14];doi: https://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html
  • Lohr B, Fingerle V, Norris DE, Hunfeld K-P. Laboratory diagnosis of Lyme borreliosis: Current state of the art and future perspectives. Crit. Rev. Clin. Lab. Sci. 2018;55:219–45. doi: 10.1080/10408363.2018.1450353
  • Wilking H, Fingerle V, Klier C, Thamm M, Stark K. Antibodies against Borrelia burgdorferi sensu lato among Adults, Germany, 2008–2011. Emerg. Infect. Dis. 2015;21:107–10. doi: 10.3201/eid2101.140009
  • Zając V, Pinkas J, Wójcik-Fatla A, Dutkiewicz J, Owoc A, Bojar I. Prevalence of serological response to Borrelia burgdorferi in farmers from eastern and central Poland. Eur. J. Clin. Microbiol. Infect. Dis. 2017;36:437–46. doi: 10.1007/s10096-016-2813-7
  • 6. Bušová A, Dorko E, Rimárová K, Diabelková J, Rovenská T, Feketeová E, et al. Seroprevalence of Lyme disease in Eastern Slovakia. Cent. Eur. J. Public Health 2018;26 Suppl:S67–71. doi: 10.21101/cejph.a5442
  • 7. Jacek E, Tang KS, Komorowski L, Ajamian M, Probst C, Stevenson B, et al. Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease. J. Immunol. Baltim. Md 1950 2016 1;196:1036–43. doi: 10.4049/jimmunol.1501861
  • Philipp MT, Bowers LC, Fawcett PT, Jacobs MB, Liang FT, Marques AR, et al. 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. 2001 1;184:870–8. doi: 10.1086/323392
  • Peltomaa M, McHugh G, Steere AC. Persistence of the antibody response to the VlsE sixth invariant region (IR6) peptide of Borrelia burgdorferi after successful antibiotic treatment of Lyme disease. J. Infect. Dis. 2003 15;187:1178–86. doi: 10.1086/374376
  • Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States. Emerg. Infect. Dis. 2016;22. doi: 10.3201/eid2207.151694
  • Seriburi V, Ndukwe N, Chang Z, Cox ME, Wormser GP. High frequency of false positive IgM immunoblots for Borrelia burgdorferi in Clinical Practice. Clin. Microbiol. Infect. 2012 1;18:1236–40. doi: 10.1111/j.1469-0691.2011.03749.x
  • Lakos A. [Lyme borreliosis--experience of the last 25 years in Hungary]. Orv. Hetil. 2009 19;150:725–32. doi: 10.1556/OH.2009.28576
  • Kalish RA, McHugh G, Granquist J, Shea B, Ruthazer R, Steere AC. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2001 15;33:780–5. doi: 10.1086/322669
  • Lakos A, Reiczigel J, Solymosi N. The positive predictive value of Borrelia burgdorferi serology in the light of symptoms of patients sent to an outpatient service for tick-borne diseases. Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al 2010;59:959–64. doi: 10.1007/s00011-010-0209-1
Year 2020, Volume: 5 Issue: 3, 85 - 93, 30.09.2020

Abstract

Project Number

EB/14/2019 (license number by Institutional Commitee of Science and Research Ethics)

References

  • Eldin C, Raffetin A, Bouiller K, Hansmann Y, Roblot F, Raoult D, et al. Review of European and American guidelines for the diagnosis of Lyme borreliosis. Médecine Mal. Infect. 2019 1;49:121–32. doi: 10.1016/j.medmal.2018.11.011
  • Two-step Laboratory Testing Process | Lyme Disease | CDC [Internet]. 2018 21 [cited 2019 14];doi: https://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html
  • Lohr B, Fingerle V, Norris DE, Hunfeld K-P. Laboratory diagnosis of Lyme borreliosis: Current state of the art and future perspectives. Crit. Rev. Clin. Lab. Sci. 2018;55:219–45. doi: 10.1080/10408363.2018.1450353
  • Wilking H, Fingerle V, Klier C, Thamm M, Stark K. Antibodies against Borrelia burgdorferi sensu lato among Adults, Germany, 2008–2011. Emerg. Infect. Dis. 2015;21:107–10. doi: 10.3201/eid2101.140009
  • Zając V, Pinkas J, Wójcik-Fatla A, Dutkiewicz J, Owoc A, Bojar I. Prevalence of serological response to Borrelia burgdorferi in farmers from eastern and central Poland. Eur. J. Clin. Microbiol. Infect. Dis. 2017;36:437–46. doi: 10.1007/s10096-016-2813-7
  • 6. Bušová A, Dorko E, Rimárová K, Diabelková J, Rovenská T, Feketeová E, et al. Seroprevalence of Lyme disease in Eastern Slovakia. Cent. Eur. J. Public Health 2018;26 Suppl:S67–71. doi: 10.21101/cejph.a5442
  • 7. Jacek E, Tang KS, Komorowski L, Ajamian M, Probst C, Stevenson B, et al. Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease. J. Immunol. Baltim. Md 1950 2016 1;196:1036–43. doi: 10.4049/jimmunol.1501861
  • Philipp MT, Bowers LC, Fawcett PT, Jacobs MB, Liang FT, Marques AR, et al. 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. 2001 1;184:870–8. doi: 10.1086/323392
  • Peltomaa M, McHugh G, Steere AC. Persistence of the antibody response to the VlsE sixth invariant region (IR6) peptide of Borrelia burgdorferi after successful antibiotic treatment of Lyme disease. J. Infect. Dis. 2003 15;187:1178–86. doi: 10.1086/374376
  • Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States. Emerg. Infect. Dis. 2016;22. doi: 10.3201/eid2207.151694
  • Seriburi V, Ndukwe N, Chang Z, Cox ME, Wormser GP. High frequency of false positive IgM immunoblots for Borrelia burgdorferi in Clinical Practice. Clin. Microbiol. Infect. 2012 1;18:1236–40. doi: 10.1111/j.1469-0691.2011.03749.x
  • Lakos A. [Lyme borreliosis--experience of the last 25 years in Hungary]. Orv. Hetil. 2009 19;150:725–32. doi: 10.1556/OH.2009.28576
  • Kalish RA, McHugh G, Granquist J, Shea B, Ruthazer R, Steere AC. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2001 15;33:780–5. doi: 10.1086/322669
  • Lakos A, Reiczigel J, Solymosi N. The positive predictive value of Borrelia burgdorferi serology in the light of symptoms of patients sent to an outpatient service for tick-borne diseases. Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al 2010;59:959–64. doi: 10.1007/s00011-010-0209-1
There are 14 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

András Zóka

Márton Gönczy This is me

Veronika Barbai This is me

Radka Nikolova

Eszter Ujhelyi This is me

Zsuzsa Kienle This is me

Gabriella Bekő This is me

Project Number EB/14/2019 (license number by Institutional Commitee of Science and Research Ethics)
Publication Date September 30, 2020
Published in Issue Year 2020 Volume: 5 Issue: 3

Cite

APA Zóka, A., Gönczy, M., Barbai, V., Nikolova, R., et al. (2020). Testing for Lyme borreliosis: could serology tell more?. Journal of Immunology and Clinical Microbiology, 5(3), 85-93.
AMA Zóka A, Gönczy M, Barbai V, Nikolova R, Ujhelyi E, Kienle Z, Bekő G. Testing for Lyme borreliosis: could serology tell more?. J Immunol Clin Microbiol. September 2020;5(3):85-93.
Chicago Zóka, András, Márton Gönczy, Veronika Barbai, Radka Nikolova, Eszter Ujhelyi, Zsuzsa Kienle, and Gabriella Bekő. “Testing for Lyme Borreliosis: Could Serology Tell More?”. Journal of Immunology and Clinical Microbiology 5, no. 3 (September 2020): 85-93.
EndNote Zóka A, Gönczy M, Barbai V, Nikolova R, Ujhelyi E, Kienle Z, Bekő G (September 1, 2020) Testing for Lyme borreliosis: could serology tell more?. Journal of Immunology and Clinical Microbiology 5 3 85–93.
IEEE A. Zóka, M. Gönczy, V. Barbai, R. Nikolova, E. Ujhelyi, Z. Kienle, and G. Bekő, “Testing for Lyme borreliosis: could serology tell more?”, J Immunol Clin Microbiol, vol. 5, no. 3, pp. 85–93, 2020.
ISNAD Zóka, András et al. “Testing for Lyme Borreliosis: Could Serology Tell More?”. Journal of Immunology and Clinical Microbiology 5/3 (September 2020), 85-93.
JAMA Zóka A, Gönczy M, Barbai V, Nikolova R, Ujhelyi E, Kienle Z, Bekő G. Testing for Lyme borreliosis: could serology tell more?. J Immunol Clin Microbiol. 2020;5:85–93.
MLA Zóka, András et al. “Testing for Lyme Borreliosis: Could Serology Tell More?”. Journal of Immunology and Clinical Microbiology, vol. 5, no. 3, 2020, pp. 85-93.
Vancouver Zóka A, Gönczy M, Barbai V, Nikolova R, Ujhelyi E, Kienle Z, Bekő G. Testing for Lyme borreliosis: could serology tell more?. J Immunol Clin Microbiol. 2020;5(3):85-93.

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