Testing for Lyme borreliosis: could serology tell more?

Yıl 2020, Cilt: 5 Sayı: 3, 85 - 93, 30.09.2020

András Zóka , Márton Gönczy Veronika Barbai Radka Nikolova , Eszter Ujhelyi Zsuzsa Kienle Gabriella Bekő

Öz

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.

Anahtar Kelimeler

serology, Lyme borreliosis, differential diagnosis

Destekleyen Kurum

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

Proje Numarası

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

Kaynakça

• 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