Abstract
Cerebrospinal fluid (CSF) and serum samples of 47 patients with serologically proven neuroborreliosis were examined by Western blotting for antibodies to a crude extract of human cortex (CNS) comprising a multitude (> 40) of protein bands. Intrathecal synthesis of total immunoglobulins was determined by the Reiber formula and of autoantibodies to CNS proteins by enzyme-linked immunoassay (ELISA) and by Western blotting. Employing ELISA, intrathecal synthesis of autoantibodies (IgG, IgM and/or IgA) was demonstrated in 40 of 47 patients with neuroborreliosis (85%), in 5 of 40 with multiple sclerosis (12%), and in 22 of 40 with viral meningoencephalitis (55%). Of 40, 35 and 15 patients with neuroborreliosis and an intrathecal synthesis of total IgG, IgM or IgA, 20 revealed an intrathecal production of IgG antibodies (50%), 24 of IgM antibodies (68%) and 6 of IgA autoantibodies (40%) in the CSF. The specificity of autoantibodies differed greatly between most patients. Of 24 different CNS proteins which elicited an immune response in various patients, identities could be determined only for the myelin basic protein (5 of 40) and for the three neurofilament proteins (NF-68, NF-150, NF-200) (13 of 40 patients). In this limited number of patients no significant correlation between individual clinical symptoms and certain autoantibodies could be detected. The higher frequency of intrathecally produced autoantibodies in patients with neuroborreliosis is assumed to result from mitogenic rather than specific activation of autoreactive B-cell clones byBorrelia burgdorferi. The pathogenic relevance of these autoantibodies remains to be determined.
Similar content being viewed by others
References
Aberer E, Brunner C, Suchanek G, Klade H, Barbour A, Stanek G, Lassmann H (1989) Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdoreri and human tissue. Ann Neurol 26:732–737
Baig S, Olsson T, Höjeberg B, Link H (1991) Cells secreting antibodies to myelin basic protein in cerebrospinal fluid in patients with Lyme neuroborreliosis. Neurology 41:581–587
Biedler JI, Helson I, Spengler BA (1973) Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res 33:2643–2652
Chou CH, Tourtellotte WW, Kibler RF (1983) Failure to detect antibodies to myelin basic protein or peptic fragments of myelin basic protein in CSF of patients with MS. Neurology 33:24–28
Comola M, Nemni R, Sher E, Qattrini A, Faravelli A, Comi G, Corbo M, Clementi F, Canal N (1993) Lambert-Eaton myasthenic syndrome and polyneuropathy in a patient with epidermoid carcinoma of the lung. Eur Neurol 33:121–125
Drlicek M, Liszka U, Jellinger K, Mohn-Staudner A, Lintner F, Grisold W (1992) Circulating antineuronal antibodies reach neurons in vivo: an autopsy study. J Neurol 239:407–410
Fabian R (1990) Uptake of antineuronal IgM by CNS neurons. Comparison with antineuronal IgG. Neurology 40:419–422
Fikrig E, Berland R, Chen M, Williams S, Sigal L, Flavell R (1993) Serologic response to theBorrelia burgdorferi flagellin demonstrates an epitope common to a neuroblastoma cell line. Proc Natl Acad Sci USA 90:183–187
Garcia-Monco JC, Coleman JL, Benach JL (1988) Antibodies to myelin protein in Lyme disease. J Infect Dis 158:667–668
Halperin J, Volkman D, Wu P (1991) Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 41:1571–1582
Hansen K, Cruz M, Link H (1990) Oligoclonal Borrelia burgdof feri-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 161:1194–1202
Hirano T, Akira S, Tage T, Kishimoto T (1990) Biological and clinical aspects of interleukin 6. Immunol Today 11:443–449
Kaiser R (1991) Affinity immunoblotting: rapid and sensitive detection of oligoclonal IgG, IgA and IgM in unconcentrated CSF by agarose isoelectric focusing. J Neurol Sci 103:216–225
Kaiser R (1994) Variable CSF findings in early and late Lyme neuroborreliosis: a follow-up study in 47 patients. JNeurol 242:26–36
Kaiser R, Lucking CH (1993) Intrathecal synthesis of specific antibodies in neuroborreliosis. Comparison of different ELISA-techniques and calculation methods. J Neurol Sci 118:64–72
Kristoferitsch W, Sluga E, Graf M, Partsch H, Neumann R, Stanek G, Budka H (1988) Neuropathy associated with aerodermatitis chronica atrophicans. Ann N Y Acad Sci 539:35–45
Martin R, Ortlauf J, Sticht-Groh V, Bogdan U, Goldmann SF, Mertens HG (1988)Borrelia burgdorferi-specific and autoreactive T-cell lines from cerebrospinal fluid in Lyme radiculomyelitis. Ann Neurol 24:509–516
Meier C, Grehl H (1988) Vaskulitische Neuropathie bei Garin-Bujadoux-Bannwarth Syndrom. Deutsche Med Wochenschr 113:135–138
Nemni R, Feltri M, Fazio R, Quattrini A, Lorenzetti I, Corbo M, Canal N (1990) Axonal neuropathy with monoclonal IgG kappa that binds to a neurofilament protein. Ann Neurol 28:361–364
Noetzel M, Cawley L, James V, Minard B, Agrawal H (1987) Anti-neurofilament protein antibodies in opsoclonus-myoclonus. J Neuroimmunol 15:137–145
Olsson T, Baig S, Höjeberg B, Link H (1990) Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis. Ann Neurol 27:132–136
Plioplys AV, Thibault J, Bouchard JP, Cockburn C, Hawkes R (1987) Anti-CNS antibodies in neurological and psychiatric disorders. J Neurol Neurosurg Psychiatry 50:1514–1521
Reiber HO, Felgenhauer K (1987) Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the Immoral immune response within the central nervous system. Clin Chim Acta 163:319–328
Roitt IM, Hutchings PR, Dawe KI, Sumar N, Bodman KB, Cooke A (1992) The forces driving autoimmune disease. J Autoimmun [Suppl A] 5:11–26
Ryberg B, Hindfelt B, Nilsson B, Olsson JE (1984) Antineural antibodies in Guillain-Barré syndrome and lymphocytic meningoradiculitis (Bannwarth's syndrome). Arch Neurol 41:1277–1281
Schoenfeld R, Araneo B, Ma Y, Yang L, Weis JJ (1992) Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen,Borrelia burgdorferi. Infect Immun 60:455–464
Sigal L, Tatum A (1988) Lyme disease patients' serum contains IgM antibodies toBorrelia burgdorferi that crossreact with neuronal antigens. Neurology 38:1439–1442
Steere AC (1989) Lyme disease. N Engl J Med 321:586–596
Stefansson K, Marton L, Dieperink M, Molnar G, Schlaepfer W, Helgason C (1985) Circulating autoantibodies to the 200,000-dalton protein of neurofilaments in the serum of healthy individuals. Science 235:1117–1119
Suchanek G, Kristoferisch W, Stanek G, Bernheimer H (1986) Anti-myelin antibodies in CSF and serum of patients with meningopolyneuritis Garin-Bujadoux-Bannwarth and other neurological diseases. Zentralbl Bakteriol Hyg A 263:160–168
Ternyinck T, Bleux C, Gregoire J, Avrameas S, Kanellopoulos-Langewin C (1990) Comparison between autoantibodies arising during Trypanosoma cruzi infection in mice and natural autoantibodies. J Immunol 44:1504–1511
Toh B, Gibbs C, Gajdusek D, Goudsmith J, Dahl (1985) The 200- and 150 kDa neurofilament protein react with IgG autoantibodies from patients with Kuru, Creutzfeldt-Jakob disease, and other neurologic disorders. Proc Natl Acad Sci USA 82:3485–3489
Weller M, Stevens A, Sommer N, Wiethölter H, Dichgans J (1991) Cerebrospinal fluid interleukins, immunoglobulins, and fibronectin in neuroborreliosis. Arch Neurol 48:837–841
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kaiser, R. Intrathecal immune response in patients with neuroborreliosis: specificity of antibodies for neuronal proteins. J Neurol 242, 319–325 (1995). https://doi.org/10.1007/BF00878875
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00878875