The intrathecal synthesis of borrelial-specific IgM- and IgG-antibodies was studied in 67 patients with neuroborreliosis and in 14 patients with neurosyphilis (controls). Antibody concentrations in serum and in the cerebrospinal fluid were determined by an enzyme immunoassay (EIA) using, as antigens, a sonicate ofBorrelia burgdorferi, the recombinant 14 kDa flagellin fragment, the outer surface protein C (22 kDa), and the high molecular mass protein p83 (83 kDa). In the sonicate EIA, IgG- and/or IgM-antibodies toBorrelia burgdorferi in serum were detected in all patients with neuroborreliosis and in 71% of patients with neurosyphilis. Intrathecal synthesis of borrelial-specific IgG- and/or IgM-antibodies was demonstrated in 82% of patients with neuroborreliosis and in 71% of patients with neurosyphilis. Immunoglobulin G- and/or IgM-antibodies in serum against any of the recombinant antigens were detected in 92% of patients with neuroborreliosis and in none of those with neurosyphilis. Intrathecal synthesis of IgG- and/or IgM-antibodies to individual recombinant antigens was demonstrated in 67% of patients with neuroborreliosis and in none of those with neurosyphilis. The sensitivity of the recombinant antigens in serum was almost equal to that of the sonicate EIA, whereas the recombinant antigens were clearly less sensitive in the estimation of the intrathecal specific immune response. It was concluded that in suspected cases of neuroborreliosis, the estimation of high specific antibodies in the recombinant EIA will be helpful in confirming the diagnosis.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Garcia-Monco JC, Benach JL: Lyme neuroborreliosis. Annals of Neurology (1995) 37:691–702.
Hansen K, Lebech AM: The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985–1990. A prospective study of 187 patients withBorrelia burgdorferi specific intrathecal antibody production. Brain (1992) 115:399–423.
Finkel MF, Halperin JJ: Nervous system Lyme borreliosis-revisited (corrected; erratum to be published) (see comments). Archives of Neurology (1992) 49:102–107.
Tumani H, Nolker G, Reiber H.: Relevance of cerebrospinal fluid variables for early diagnosis of neuroborreliosis. Neurology (1995) 45:1663–1670.
Steere AC, Berardi VP, Weeks KE, Logigian EL, Ackermann R: Evaluation of the intrathecal antibody response toBorrelia burgdorferi as a diagnostic test for Lyme neuroborreliosis. Journal of Infectious Diseases (1990) 161:1203–1209.
Hammers-Berggren S, Hansen K, Lebech AM, Karlsson M:Borrelia burgdorferi-specific intrathecal antibody production in neuroborreliosis: a follow-up study. Neurology (1993) 43:169–175.
Kaiser R: Variable CSF findings in early and late Lyme neuroborreliosis: a follow-up study in 47 patients. Journal of Neurology (1994) 242:26–36.
Halperin JJ, Logigian EL, Finkel MF, Pearl RA: Practice parameters for the diagnosis of patients with nervous system Lyme borreliosis (Lyme disease). Quality Standards Subcommittee of the American Academy of Neurology. Neurology (1996) 46:619–627.
Hansen K: Laboratory diagnostic methods in Lyme borreliosis. Clinics in Dermatology (1993) 11:407–414.
Barbour AG: Laboratory aspects of Lyme borreliosis. Clinical Microbiology Reviews (1988) 1:399–414.
Feder HM, Jr., Gerber MA, Luger SW, Ryan RW: False positive serologic tests for Lyme disease after varicella infection. New England Journal of Medicine (1991) 325:1886–1887.
Bruckbauer HR, Preac-Mursic V, Fuchs R, Wilske B: Cross-reactive proteins ofBorrelia burgdorferi. European Journal of Clinical Microbiology & Infectious Diseases (1992) 11:224–232.
Magnarelli LA, Anderson JF, Johnson RC: Cross-reactivity in serological tests for Lyme disease and other spirochetal infections. Journal of Infectious Diseases (1987) 156:183–188.
Kaiser R: Intrathecal immune response in neuroborreliosis: importance of cross-reactive antibodies. International Journal of Medical Microbiology, Virology, Parasitology, and Infectious Diseases (1995) 282:303–314.
Rauer S, Kayser M, Neubert U, Rasiah C, Vogt A: Establishment of enzyme-linked immunosorbent assay using purified recombinant 83-kilodalton antigen ofBorrelia burgdorferi sensu stricto andBorrelia afzelii for serodiagnosis of Lyme disease. Journal of Clinical Microbiology (1995) 33: 2596–2600.
Rasiah C, Schiltz E, Reichert J, Vogt A: Purification and characterization of a tryptic peptide ofBorrelia burgdorferi flagellin, which reduces cross-reactivity in immunoblots and ELISA. Journal of General Microbiology (1992) 138: 147–154.
Fikrig E, Huguenel ED, Berland R, Rahn DW, Hardin JA, Flavell RA: Serologic diagnosis of Lyme disease using recombinant outer surface proteins A and B and flagellin. Journal of Infectious Diseases (1992) 165:1127–1132.
Wilske B, Fingerle V, Herzer P, Hofmann A, Lehnert G, Peters H, Pfister HW, Preac-Mursic V, Soutschek E, Weber K.: Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Comparison with indirect immunofluorescence and enzyme-linked immunosorbent assay. Medical Microbiology and Immunolology (1993) 182:255–270.
Hansen K, Hindersson P, Pedersen NS: Measurement of antibodies to theBorrelia burgdorferi flagellum improves serodiagnosis in Lyme disease. Journal of Clinical Microbiology (1988) 26:338–346.
Hansen K, Lebech AM: Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis ofBorrelia burgdorferi-specific immunoglobulin G, A, and M. Annals of Neurology (1991) 30:197–205.
Kaiser R, Rasiah C, Gassmann G, Vogt A, Lucking CH: Intrathecal antibody synthesis in Lyme neuroborreliosis: use of recombinant p41 and a 14-kDa flagellin fragment in ELISA. Journal of Medical Microbiology (1993) 39:290–297.
Padula SJ, Sampieri A, Dias F, Szczepanski A, Ryan RW: Molecular characterization and expression of p23 (OspC) from a North American strain ofBorrelia burgdorferi. Infection and Immunity (1993) 61:5097–5105.
Wilske B, Preac-Mursic V, Schierz G, von Busch K: Immunochemical and immunological analysis of EuropeanBorrelia burgdorferi strains. Zentralblatt für Bakteriologie, Mikrobiologie, und Hygiene (A) (1986) 263:92–102.
Wilske B, Preac-Mursic V, Schierz G, Liegl G, Gueye W: Detection of IgM and IgG antibodies toBorrelia burgdorferi using different strains as antigen. Zentralblatt für Bakteriologie, Mikrobiologie, und Hygiene (1989) 18:299–399.
Engstrom SM, Shoop E, Johnson RC: Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. Journal of Clinical Microbiology (1995) 33:419–427.
Coleman JL, Benach JL: Isolation of antigenic components from the Lyme disease spirochete: their role in early diagnosis. Journal of Infectious Diseases (1987) 155:756–765.
Zoller L, Cremer J, Faulde M: Western blot as a tool in the diagnosis of Lyme borreliosis. Electrophoresis (1993) 14:937–944.
Ditton HJ, Neuss M, Zoller L: Evidence thatBorrelia burgdorferi immunodominant proteins p100, p94 and p83 are identical. FEMS Microbiology Letters (1992) 73:217–220
Jauris-Heipke S, Fuchs R, Hofmann A, Lottspeich F, Preac-Mursic V, Soutschek E, Will G, Wilske B: Molecular characterization of the p100 gene ofBorrelia burgdorferi strain PKo. FEMS Microbiology Letters (1993) 114:235–241.
Luft BJ, Mudri S, Jiang W, Dattwyler RJ, Gorevic PD, Fischer T, Munoz P, Dunn JJ, Schubach WH: The 93-kilodalton protein ofBorrelia burgdorferi: an immunodominant protoplasmic cylinder antigen. Infection and Immunity (1992) 60:4309–4321.
Perng GC, LeFebvre RB, Johnson RC: Further characterization of a potent immunogen and the chromosomal gene encoding it in the Lyme disease agent,Borrelia burgdorferi. Infection and Immunity (1991) 59:2070–2074.
Volkman DJ, Luft BJ, Gorevic PD, Schultz J, Padovano L: Characterization of an immunoreactive 93-kDa core protein ofBorrelia burgdorferi with a human IgG monoclonal antibody. Journal of Immunology (1991) 146:3177–3182.
Rasiah C, Rauer S, Gassmann GS, Vogt A: Use of a hybrid protein consisting of the variable region of theBorrelia burgdorferi flagellin and part of the 83-kDa protein as antigen for serodiagnosis of Lyme disease. Journal of Clinical Microbiology (1994) 32:1011–1017.
Kaiser R, Lucking CH: Intrathecal synthesis of specific antibodies in neuroborreliosis. Comparison of different ELISA techniques and calculation methods. Journal of Neurological Sciences (1993) 118:64–72.
Müller F, Moskophidis M, Borkhard HL: Detection of immunoglobulin M antibodies toTreponema pallidum in a modified immunosorbent assay. European Journal of Clinical Microbiology (1987) 6:35–39.
Reiber H, Lange P: Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clinical Chemistry (1991) 37:1153–1160.
Gerber MA, Shapiro ED, Bell GL, Sampieri A, Padula SJ: Recombinant outer surface protein C ELISA for the diagnosis of early Lyme disease. Journal of Infectious Diseases (1995) 171:724–727.
Wilske B, Fingerle V, Preac-Mursic V, Jauris-Heipke S, Hofmann A, Loy H, Pfister HW, Rossler D, Soutschek E: Immunoblot using recombinant antigens derived from different genospeciesof Borrelia burgdorferi sensu lato. Medical Microbiology and Immunology (1994) 183:43–59.
Stiernstedt G, Dattwyler R, Duray PH, Hansen K, Jirous J, Johnson RC, Karlsson M, Preac-Mursic V, Schwan TG: Diagnostic tests in Lyme borreliosis. Scandinavian Journal of Infectious Diseases (1991) 77 Supplement: 136–142.
Kruger H, Reuss K, Pulz M, Rohrbach E, Pflughaupt KW, Martin R, Mertens HG: Meningoradiculitis and encephalomyelitis due toBorrelia burgdorferi: a follow-up study of 72 patients over 27 years. Journal of Neurology (1989) 236:322–328.
Huycke MM, D'Alessio DD, Marx JJ: Prevalence of antibody toBorrelia burgdorferi by indirect fluorescent antibody assay, ELISA, and western immunoblot in healthy adults in Wisconsin and Arizona. Journal of Infectious Diseases (1992) 165:1133–1137.
About this article
Cite this article
Kaiser, R., Rauer, S. Analysis of the intrathecal immune response in neuroborreliosis to a sonicate antigen and three recombinant antigens ofBorrelia burgdorferi sensu stricto. Eur. J. Clin. Microbiol. Infect. Dis. 17, 159–166 (1998). https://doi.org/10.1007/BF01691111
- Borrelia burgdorferi
- Recombinant proteins
- Enzyme immunoassay
- Antibody index