Diagnostic use of CNS Antibodies

  • Kurt Danner
Part of the Current Topics in Veterinary Medicine and Animal Science book series (CTVM, volume 29)


Antibodies appear in the CNS either by leakage from serum through an impaired blood-CNS barrier or after local production during certain infections of the CNS, such as distemper in the dog or measles/SSPE in man. Locally produced CNS antibodies are different from serum antibodies but can be demonstrated by the same techniques. They may be taken for routine diagnosis especially when the aetiological agent is difficult to identify. Our own experiences with Borna disease in horses, sheep and rabbits are presented, since its diagnosis intra vitam and post mortem is routinely based upon demonstration of CNS antibodies. It is suggested that the method might be applicable to other viral infections of the CNS.


Multiple Sclerosis Rabies Virus Canine Distemper Virus Japanese Encephalitis Virus Subacute Sclerosing Panencephalitis 
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  1. Anzil, A.P. and Blinzinger, K. 1972. Electron microscopic studies of rabbit central and peripheral nervous system in expermental Borna disease. Acta neuropathol., 22, 305–318.PubMedCrossRefGoogle Scholar
  2. Arnadottir, T., Reunanen, M. and Salmi, A. 1982. Intrathecal synthesis of virus antibodies in multiple sclerosis patients. Infect. Immun., 38, 399–407.PubMedGoogle Scholar
  3. Beam, T.R. and Allen, J.C. 1977. Blood, brain and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges. Antimicrob. Agents Chemother., 12, 710–716.PubMedGoogle Scholar
  4. Bell, J.F. and Moore, G.J. 1979. Allergic encephalitis, rabies antibodies, and the blood/brain barrier. J. Lab. Clin. Med., 94, 5–11.PubMedGoogle Scholar
  5. Bell, J.F., Lodmell, D.L., Moore, G.J. and Raymond, G.H. 1966. Brain neutralization of rabies virus to distinguish recovered animals from previously vaccinated animals. J. Immunol., 97, 747–753.PubMedGoogle Scholar
  6. Bemmann, H. 1926. Beitrag zur pathologischen Histologie, postmortalen Diagnose und Pathogenese der seuchenhaften Gehirn-Ruckenmarks ent zundung (Bornasche Krankheit) der Pferde. Vet. Med. Dissertation, Glessen.Google Scholar
  7. Bradbury, M. 1979. Why a blood-brain barrier? Trends Neurci., 2, 36–38.CrossRefGoogle Scholar
  8. Brown, P., Cathala, F., Gajdusek, D.C. and Gibbs, C.J. 1971. Measles antibodies in the cerebrospinal fluid of patients with multiple sclerosis. Proc. Soc. Exp. Biol. Med., 137, 956–961.PubMedGoogle Scholar
  9. Brown, P., Cathala, F. and Gajdusek, D.C. 1973. Further studies of viral antibodies in the cerebrospinal fluid of patients with multiple sclerosis. Proc. Soc. Exp. Biol. Med., 143, 828–829.PubMedGoogle Scholar
  10. Burke, D.S., Nisalak, A. and Ussery, M.A. 1982. Antibody capture immunoassay detection of Japanese encephalitis virus immunoglobulin M and G antibodies in cerebrospinal fluid. J. Clin. Microbiol., 16, 1034–1042.PubMedGoogle Scholar
  11. Cappel, R., Thiry, L. and Clinet, G. 1975. Viral antibodies in the CSF after acute CNS infections. Arch. Neurol., 32, 629–631.PubMedGoogle Scholar
  12. Cserr, H.F. 1971. Physiology of the choroid plexus. Physiol. Rev., 41, 273–311.Google Scholar
  13. Danner, K. 1976. Labordiagnose der Bornaschen Krankheit über den Nachweis von Antikörpern im Zentralnervensystem. Zbl. Vet. Med. B., 23, 865–867.Google Scholar
  14. Danner, K. 1982. Borna-Virus and Borna-Infektionen: vom Miasma zum Modell. Enke, Stuttgart.Google Scholar
  15. Danner, K. and Luthgen, K. 1978. Antikörper im ZNS Borna-infizierter Tiere. Fortschr. Vet. Med., 28, 192–197.Google Scholar
  16. Deibel, R. and Schryver, G.D. 1976. Viral antibody in the cerebrospinal fluid of patients with acute central nervous system infections. J. Clin. Microbiol., 3, 397–401.PubMedGoogle Scholar
  17. Freund, J. 1930. Accumulation of antibodies in the central nervous system. J. Exp. Med., 51, 889.PubMedCrossRefGoogle Scholar
  18. Gerhard, W., Iwasaki, Y. and Koprowski, H. 1978. The central nervous system-associated immune response to parainfluenza type 1 virus in mice. J. Immunol., 120, 1256–1260.PubMedGoogle Scholar
  19. Gough, P.M., Dierks, R.E., Russell, R.M. and Archer, B.G. 1974. Characterisation of brain-associated rabies neutralising substance. J. Infect. Dis., 129, 456–460.PubMedCrossRefGoogle Scholar
  20. Haire, M. 1977. Significance of virus antibodies in multiple sclerosis. Br. Med. Bull., 33, 40–44.PubMedGoogle Scholar
  21. Hofmann, H., Frisch-Niggemeyer, W., Heinz, F. and Kunz, C.H. 1979. Immunoglobulins to tick-borne encephalitis in the cerebrospinal fluid of man. J. Med. Virol., 4, 241–245.PubMedCrossRefGoogle Scholar
  22. Kabat, E.A., Freedman, D.A., Murray, J.P. and Knaub, V. 1950. A study of the er ist al line albumin, gamma globulin and total protein in the cerebrospinal fluid of one hundred cases of multiple sclerosis. Am. J. Med. Sci., 219, 55.PubMedCrossRefGoogle Scholar
  23. Kempe, C.H., Takayashi, K., Miyamoto, H., McIntosh, K., Tourtellotte, W.W. and Adams, J.M. 1973. Elevated cerebrospinal fluid vaccinia antibodies in multiple sclerosis. Arch. Neurol., 28, 278–279.PubMedGoogle Scholar
  24. Krakowka, S., McCullough, B., Koestner, A. and Olson, R. 1973. Myelin-specific autoantibodies associated with central nervous system demyelination in canine distemper virus infection. Infect. Immunol., 8, 819–827.Google Scholar
  25. Krey, H.F., Ludwig, H. and Boschek, C.B. 1979. Multifocal retinopathy in Borna disease virus infected rabbits. Amer. J. Ophthalmol., 87, 157–164.Google Scholar
  26. Kubes, V. and Gallis, F. 1944. Brain tissue neutralisation, a new biological reaction for rabies virus. Can. J. Comp. Med., 8, 48–60.PubMedGoogle Scholar
  27. Laterre, E.C. 1974. Cerebrospinal fluid in pathology. La Ricerca Clin. Lab., 4, 540–566.Google Scholar
  28. Lebon, P., Schuller, E., Marteau, R. and Lhermitte, F. 1976. Intrathecal rubella-antibody synthesis in multiple sclerosis. Lancet 1, 689–690.PubMedCrossRefGoogle Scholar
  29. Link, H. and Zettervall, O. 1970. Multiple sclerosis: disturbed kappa: lambda light chain ratio of immunoglobulin G in cerebrospinal fluid. Clin. Exp. Immunol., 6, 435–438.PubMedGoogle Scholar
  30. Ludwig, H. and Thein, P. 1977. Demonstration of specific antibodies in the central nervous system of horses naturally infected with Borna disease. Med. Microbiol. Immunol., 163, 215–226.PubMedCrossRefGoogle Scholar
  31. Ludwig, H., Koester, V., Pauli, G. and Rott, R. 1977. The cerebrospinal fluid of rabbits infected with Borna disease virus. Arch. Virol., 55, 209–223.PubMedCrossRefGoogle Scholar
  32. Luthgen, K. 1977. Untersuchungen über Nachweis, Bildung und Vorkommen von Bornavirus-Antikörpern. Vet. Med. Dissertation, Munchen.Google Scholar
  33. Mattson, D.H., Roos, R.P. and Arnason, B.G.W. 1980. Isoelectric focusing of I eluted from multiple sclerosis and subacute sclerosing panencephalitis brains. Nature, 287, 335–337.PubMedCrossRefGoogle Scholar
  34. Mayr, A. and Danner, K. 1972. Production of Borna virus in tissue culture. Proc. Soc. Exp. Biol. Med., 140, 511–515.PubMedGoogle Scholar
  35. Mayr, A. and Danner, K. 1974. Zuchtung und Titrierung von Borna-Virus in Zellkulturen aus Organen fötaler Lammer. Zbl. Vet. Med. B., 21, 131–137.Google Scholar
  36. Metzler, A. 1977. Die Diagnose der naturlichen Bornavirus-Infektion bei Schafen und Pferden. Ein Vergleich verschiedener Methoden. Vet. Med. Dissertation, Zurich.Google Scholar
  37. Metzler, A., Frei, U. and Danner, K. 1976. Virologisch gesicherter Ausbruch der Bornaschen Krankheit in einer Schafherde der Schweiz. Schweiz. Arch. Tierheilk., 118, 483–492.Google Scholar
  38. Metzler, A., Ehrensperger, F. and Wyler, R. 1978. Naturliche Bornavirus-Infektion beim Kaninchen. Zbl. Vet. Med. B., 25, 161–164.Google Scholar
  39. Metzler, A., Ehrensperger, F. and Danner, K. 1979. Bornavirus-Infektion bei Schafen: Verlaufsuntersuchungen nach spontaner Infektion, unter besonderer Berücksichtigung der Antikorperkinetik im Serum und Liquor cerebrospinalis. Schweiz. Arch. Tierheilk., 121, 37–48.Google Scholar
  40. Morgan, I.A. 1947. The role of antibody in experimental poliomyelitis. III. Distribution of antibody in and out of the central nervous system in paralysed monkeys. Am. J. Hyg., 45, 390.PubMedGoogle Scholar
  41. Nicolau, S., Galloway, I.A. and Stroian, N. 1929. L’immunite dans l’encephalomyelite enzootique experimentale. C.R. Soc. Biol. Paris, 100, 607–610.Google Scholar
  42. Nordal, H.J., Vandvik, B. and Norrby, E. 1978. Multiple sclerosis: Local synthesis of electrophoretically restricted measles, rubella, mumps and herpes simplex virus antibodies in the central nervous system. Scand. J. Immunol., 7, 473–479.PubMedCrossRefGoogle Scholar
  43. Norrby, E., Salmi, A.A., Link, H., Vandvik, B., Olsson, J.-E. and Panelius, M. 1974. The measles virus antibody response in subacute sclerosing panencephalitis and multiple sclerosis. In “Slow Virus Diseases” (Eds. W. Zeman and E.H. Lennette). (Williams and Wilkins Co., Baltimore). pp. 72–85.Google Scholar
  44. Oehmichen, M. 1978. Mononuclear phagocytes in the central nervous system. (Springer, Berlin).Google Scholar
  45. Ogra, P.L. 1970. Distribution of echovirus antibody in serum, nasopharynx:, rectum and spinal fluid after natural infection with echovirus type 6. Infect. Immun., 2, 150–155.PubMedGoogle Scholar
  46. Ogra, P.L., Ogra, S.S., Al-Nakeeb, S. and Coppola, P.R. 1973. Local antibody response to experimental poliovirus infection in the central nervous system of rhesus monkeys. Infect. Immun., 2, 931–937.Google Scholar
  47. Oldstone, M.B.A., Bokisch, V.A., Dixon, F.J., Barbosa, L.H., Fucillo, D. and Sever, J.L. 1975. Subacute sclerosing panencephalitis: Destruction of human brain cells by antibody and complement in an autologous system. Clin. Immunol. Immunopathol., 4, 52–58.PubMedCrossRefGoogle Scholar
  48. Rapoport, S.I. 1976. Blood-brain barrier in physiology and medicine. (Raven Press, New York).Google Scholar
  49. Reid, H.W., Doherty, P.C. and Muslan, A. 1971. Louping ill encephalomyelitis in the sheep. III. Immunoglobulins in cerebrospinal fluid. J. Comp. Pathol., 81, 537–543.PubMedCrossRefGoogle Scholar
  50. Russell, A.S. and Saertre, A. 1976. Antibodies to herpes-simplex virus in “normal” cerebrospinal fluid. Lancet I, 64–65.CrossRefGoogle Scholar
  51. Salmi, A.A. 1973. Virus antibodies in patients with multiple sclerosis. Ann. Clin. Res., 5, 319–329.PubMedGoogle Scholar
  52. Salmi, A.A., Panelius, M., Halonen, P., Rinne, U.K. and Penttinen, K. 1972. Measles virus antibody in cerebrospinal fluids from patients with multiple sclerosis. British Med. J., 19 477–479.CrossRefGoogle Scholar
  53. Salmi, A.A., Viljanen, M. and Rennonen, M. 1981. Intrathecal synthesis of antibodies to diphtheria and tetanus toxoids in multiple sclerosis patients. J. Neuroimmunol., 1, 333–341.PubMedCrossRefGoogle Scholar
  54. Schlesinger, R.W. 1949. The mechanism of active cerebral immunity to equine encephalomyelitis virus. J. Exp. Med., 89, 507.PubMedCrossRefGoogle Scholar
  55. Schliep, G. and Felgenhauer, K. 1978. Serum-CSF protein gradients, the blood-CSF barrier and the local immune response. J. Neurol., 218, 77–96.PubMedCrossRefGoogle Scholar
  56. Schneider, L.G. and Burtscher, H. 1967. Untersuchungen über die Pathogenese der Tollwut bei Huhnern nach intracerebraler Infektion. Zbl. Vet. Med. B., 14, 598–624.Google Scholar
  57. Skoldenberg, B., Kalimo, K., Carlstrom, A., Forsgren, M. and Halonen, P. 1981. Acta Neurol. Scand., 63, 273. (Cited after Torrey et al., 1982).PubMedCrossRefGoogle Scholar
  58. Thormar, H., Wisniewski, H.M. and Lin, F.H. 1979. Sera and cerebrospinal fluids from noimal uninfected sheep contain a visna virus inhibiting factor. Nature, 279, 245–246.PubMedCrossRefGoogle Scholar
  59. Torrey, E.F., Yolken, R.H. and Winfrey, C.J. 1982. Cytomegalovirus antibody in cerebrospinal fluid of schizophrenic patients detected by enzyme immunoassay. Science, 216, 892–894.PubMedCrossRefGoogle Scholar
  60. Tsai, S.C., Summers, B.A. and Appel, M.J.G. 1982. Interferon in cerebro-spinal fluid. A marker for viral persistence in canine distemper encephalomyelitis. Arch. Virol., 72, 257–265.PubMedCrossRefGoogle Scholar
  61. Vandvik, B. 1973. Immunopathological aspects in the pathogenesis of subacute sclerosing panencephalitis, with special reference to the significance of the immune response in the central nervous system. Ann. Clin. Res., 5, 308–315.PubMedGoogle Scholar
  62. Weisner, B. 1980. Unterschiede in der Zusammensetzung von ventrikulärem und lumbalem Liquor. Selektive Funktionen an der Blut-Liquor- und Hirn-Liquor-Schranke. Lab. Med., 4, 75–80.Google Scholar
  63. Wisniewski, H.M. 1977. Immunopathology of demyelination in autoimmune diseases and virus infections. Br. Med. Bull., 33, 54–59.PubMedGoogle Scholar
  64. Yamanouchi, K., Sato, T.A., Kobune, F. and Shishido, A. 1979. Antibody responses in the cerebrospinal fluid of cynomolgus monkeys after intracerebral inoculation with paramyxoviruses. Infect. Immun., 23, 185–191.PubMedGoogle Scholar
  65. Zakay-Rones, Z., Spira, G. and Levy, R. 1974. Local antibody fonnation in the brain of chickens. Arch. Virusforsch., 45, 290–293.PubMedCrossRefGoogle Scholar

Copyright information

© ECSC, EEC, EAEC, Brussels-Luxembourg 1984

Authors and Affiliations

  • Kurt Danner
    • 1
  1. 1.Institut fur Hygiene und Infektionskrankheiten der TiereJustus Liebig-UniversitatGiessenFederal Republic of Germany

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