Skip to main content
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1996 Jan;34(1):1–9. doi: 10.1128/jcm.34.1.1-9.1996

Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.

M E Aguero-Rosenfeld 1, J Nowakowski 1, S Bittker 1, D Cooper 1, R B Nadelman 1, G P Wormser 1
PMCID: PMC228718  PMID: 8748261

Abstract

We investigated the appearance and evolution of immunoglobulin M (IgM) and IgG antibodies to Borrelia burgdorferi in 46 patients with culture-proven erythema migrans (EM). All patients received antimicrobial treatment and were prospectively evaluated for up to 1 year. A total of 257 serially collected serum samples were tested by commercial IgG-IgM enzyme-linked immunosorbent assay and separate IgM and IgG immunoblots (IBs). At the baseline, 33% of the patients had a positive ELISA result and 43% of the patients had a positive IgM IB result by using the criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors for the interpretation of IB results. Positive serology at the baseline and the rate of seroconversion correlated directly with disease duration and/or evidence of dissemination prior to treatment. At days 8 to 14 after the baseline, 91% of patients had a positive ELISA result and/or IgM IB result. Peak IgM antibody levels were seen at this time in patients with localized or disseminated disease. The most frequent IgM bands at the baseline and the peak were of 24 kDa (OspC), 41 kDa, and 37 kDa. Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors. The persistence of antibodies was directly related to disease duration and/or dissemination prior to treatment. Since IgM antibodies to the 24- and 41-kDa antigens remained detectable for long periods, 38% of IgM IBs were still positive at 1 year postbaseline. IgM to antigens of 39, 58, 60, 66, or 93 kDa, conversely, were most often seen in sera obtained within 1 month postbaseline. Their presence may be of assistance in confirming a recent infection with B. burgdorferi in individuals living in areas where Lyme disease is endemic.

Full Text

The Full Text of this article is available as a PDF (385.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguero-Rosenfeld M. E., Nowakowski J., McKenna D. F., Carbonaro C. A., Wormser G. P. Serodiagnosis in early Lyme disease. J Clin Microbiol. 1993 Dec;31(12):3090–3095. doi: 10.1128/jcm.31.12.3090-3095.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbour A. G., Hayes S. F., Heiland R. A., Schrumpf M. E., Tessier S. L. A Borrelia-specific monoclonal antibody binds to a flagellar epitope. Infect Immun. 1986 May;52(2):549–554. doi: 10.1128/iai.52.2.549-554.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbour A. G., Tessier S. L., Todd W. J. Lyme disease spirochetes and ixodid tick spirochetes share a common surface antigenic determinant defined by a monoclonal antibody. Infect Immun. 1983 Aug;41(2):795–804. doi: 10.1128/iai.41.2.795-804.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bruckbauer H. R., Preac-Mursic V., Fuchs R., Wilske B. Cross-reactive proteins of Borrelia burgdorferi. Eur J Clin Microbiol Infect Dis. 1992 Mar;11(3):224–232. doi: 10.1007/BF02098084. [DOI] [PubMed] [Google Scholar]
  5. Coleman J. L., Benach J. L. Characterization of antigenic determinants of Borrelia burgdorferi shared by other bacteria. J Infect Dis. 1992 Apr;165(4):658–666. doi: 10.1093/infdis/165.4.658. [DOI] [PubMed] [Google Scholar]
  6. Coleman J. L., Benach J. L. Isolation of antigenic components from the Lyme disease spirochete: their role in early diagnosis. J Infect Dis. 1987 Apr;155(4):756–765. doi: 10.1093/infdis/155.4.756. [DOI] [PubMed] [Google Scholar]
  7. Comstock L. E., Fikrig E., Shoberg R. J., Flavell R. A., Thomas D. D. A monoclonal antibody to OspA inhibits association of Borrelia burgdorferi with human endothelial cells. Infect Immun. 1993 Feb;61(2):423–431. doi: 10.1128/iai.61.2.423-431.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Craft J. E., Fischer D. K., Shimamoto G. T., Steere A. C. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness. J Clin Invest. 1986 Oct;78(4):934–939. doi: 10.1172/JCI112683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dattwyler R. J., Volkman D. J., Luft B. J., Halperin J. J., Thomas J., Golightly M. G. Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. N Engl J Med. 1988 Dec 1;319(22):1441–1446. doi: 10.1056/NEJM198812013192203. [DOI] [PubMed] [Google Scholar]
  10. Dressler F., Whalen J. A., Reinhardt B. N., Steere A. C. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993 Feb;167(2):392–400. doi: 10.1093/infdis/167.2.392. [DOI] [PubMed] [Google Scholar]
  11. Engstrom S. M., Shoop E., Johnson R. C. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol. 1995 Feb;33(2):419–427. doi: 10.1128/jcm.33.2.419-427.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fawcett P. T., Gibney K. M., Rose C. D., Dubbs S. B., Doughty R. A. Frequency and specificity of antibodies that crossreact with Borrelia burgdorferi antigens. J Rheumatol. 1992 Apr;19(4):582–587. [PubMed] [Google Scholar]
  13. Feder H. M., Jr, Gerber M. A., Luger S. W., Ryan R. W. Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease. Clin Infect Dis. 1992 Nov;15(5):788–793. doi: 10.1093/clind/15.5.788. [DOI] [PubMed] [Google Scholar]
  14. Fuchs R., Jauris S., Lottspeich F., Preac-Mursic V., Wilske B., Soutschek E. Molecular analysis and expression of a Borrelia burgdorferi gene encoding a 22 kDa protein (pC) in Escherichia coli. Mol Microbiol. 1992 Feb;6(4):503–509. doi: 10.1111/j.1365-2958.1992.tb01495.x. [DOI] [PubMed] [Google Scholar]
  15. Grodzicki R. L., Steere A. C. Comparison of immunoblotting and indirect enzyme-linked immunosorbent assay using different antigen preparations for diagnosing early Lyme disease. J Infect Dis. 1988 Apr;157(4):790–797. doi: 10.1093/infdis/157.4.790. [DOI] [PubMed] [Google Scholar]
  16. Hammers-Berggren S., Lebech A. M., Karlsson M., Svenungsson B., Hansen K., Stiernstedt G. Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis. J Clin Microbiol. 1994 Jun;32(6):1519–1525. doi: 10.1128/jcm.32.6.1519-1525.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karlsson M., Möllegård I., Stiernstedt G., Wretlind B. Comparison of Western blot and enzyme-linked immunosorbent assay for diagnosis of Lyme borreliosis. Eur J Clin Microbiol Infect Dis. 1989 Oct;8(10):871–877. doi: 10.1007/BF01963773. [DOI] [PubMed] [Google Scholar]
  18. Luft B. J., Gorevic P. D., Jiang W., Munoz P., Dattwyler R. J. Immunologic and structural characterization of the dominant 66- to 73-kDa antigens of Borrelia burgdorferi. J Immunol. 1991 Apr 15;146(8):2776–2782. [PubMed] [Google Scholar]
  19. Luft B. J., Mudri S., Jiang W., Dattwyler R. J., Gorevic P. D., Fischer T., Munoz P., Dunn J. J., Schubach W. H. The 93-kilodalton protein of Borrelia burgdorferi: an immunodominant protoplasmic cylinder antigen. Infect Immun. 1992 Oct;60(10):4309–4321. doi: 10.1128/iai.60.10.4309-4321.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ma B., Christen B., Leung D., Vigo-Pelfrey C. Serodiagnosis of Lyme borreliosis by western immunoblot: reactivity of various significant antibodies against Borrelia burgdorferi. J Clin Microbiol. 1992 Feb;30(2):370–376. doi: 10.1128/jcm.30.2.370-376.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Magnarelli L. A. Quality of Lyme disease tests. JAMA. 1989 Dec 22;262(24):3464–3465. [PubMed] [Google Scholar]
  22. Massarotti E. M., Luger S. W., Rahn D. W., Messner R. P., Wong J. B., Johnson R. C., Steere A. C. Treatment of early Lyme disease. Am J Med. 1992 Apr;92(4):396–403. doi: 10.1016/0002-9343(92)90270-l. [DOI] [PubMed] [Google Scholar]
  23. Mitchell P. D., Reed K. D., Aspeslet T. L., Vandermause M. F., Melski J. W. Comparison of four immunoserologic assays for detection of antibodies to Borrelia burgdorferi in patients with culture-positive erythema migrans. J Clin Microbiol. 1994 Aug;32(8):1958–1962. doi: 10.1128/jcm.32.8.1958-1962.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Padula S. J., Dias F., Sampieri A., Craven R. B., Ryan R. W. Use of recombinant OspC from Borrelia burgdorferi for serodiagnosis of early Lyme disease. J Clin Microbiol. 1994 Jul;32(7):1733–1738. doi: 10.1128/jcm.32.7.1733-1738.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Padula S. J., Sampieri A., Dias F., Szczepanski A., Ryan R. W. Molecular characterization and expression of p23 (OspC) from a North American strain of Borrelia burgdorferi. Infect Immun. 1993 Dec;61(12):5097–5105. doi: 10.1128/iai.61.12.5097-5105.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schwan T. G., Burgdorfer W. Antigenic changes of Borrelia burgdorferi as a result of in vitro cultivation. J Infect Dis. 1987 Nov;156(5):852–853. doi: 10.1093/infdis/156.5.852-a. [DOI] [PubMed] [Google Scholar]
  27. Schwan T. G., Schrumpf M. E., Karstens R. H., Clover J. R., Wong J., Daugherty M., Struthers M., Rosa P. A. Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi, isolated from ticks throughout California. J Clin Microbiol. 1993 Dec;31(12):3096–3108. doi: 10.1128/jcm.31.12.3096-3108.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schwan T. G., Simpson W. J. Factors influencing the antigenic reactivity of Borrelia burgdorferi, the Lyme disease spirochete. Scand J Infect Dis Suppl. 1991;77:94–101. [PubMed] [Google Scholar]
  29. Shrestha M., Grodzicki R. L., Steere A. C. Diagnosing early Lyme disease. Am J Med. 1985 Feb;78(2):235–240. doi: 10.1016/0002-9343(85)90432-2. [DOI] [PubMed] [Google Scholar]
  30. Simpson W. J., Schrumpf M. E., Schwan T. G. Reactivity of human Lyme borreliosis sera with a 39-kilodalton antigen specific to Borrelia burgdorferi. J Clin Microbiol. 1990 Jun;28(6):1329–1337. doi: 10.1128/jcm.28.6.1329-1337.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Steere A. C., Grodzicki R. L., Kornblatt A. N., Craft J. E., Barbour A. G., Burgdorfer W., Schmid G. P., Johnson E., Malawista S. E. The spirochetal etiology of Lyme disease. N Engl J Med. 1983 Mar 31;308(13):733–740. doi: 10.1056/NEJM198303313081301. [DOI] [PubMed] [Google Scholar]
  32. Sădziene A., Rosa P. A., Thompson P. A., Hogan D. M., Barbour A. G. Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization. J Exp Med. 1992 Sep 1;176(3):799–809. doi: 10.1084/jem.176.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wilske B., Jauris-Heipke S., Lobentanzer R., Pradel I., Preac-Mursic V., Rössler D., Soutschek E., Johnson R. C. Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype. J Clin Microbiol. 1995 Jan;33(1):103–109. doi: 10.1128/jcm.33.1.103-109.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wilske B., Preac-Mursic V., Jauris S., Hofmann A., Pradel I., Soutschek E., Schwab E., Will G., Wanner G. Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi. Infect Immun. 1993 May;61(5):2182–2191. doi: 10.1128/iai.61.5.2182-2191.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wilske B., Preac-Mursic V., Schierz G., Busch K. V. Immunochemical and immunological analysis of European Borrelia burgdorferi strains. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):92–102. doi: 10.1016/s0176-6724(86)80108-0. [DOI] [PubMed] [Google Scholar]
  36. Zöller L., Burkard S., Schäfer H. Validity of western immunoblot band patterns in the serodiagnosis of Lyme borreliosis. J Clin Microbiol. 1991 Jan;29(1):174–182. doi: 10.1128/jcm.29.1.174-182.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES