Acta Neuropathologica

, Volume 89, Issue 4, pp 341–345 | Cite as

Uptake of systemically administered human anticerebellar antibody by rat Purkinje cells following blood-brain barrier disruption

  • John E. Greenlee
  • James B. Burns
  • J. W. Rose
  • Kurt A. Jaeckle
  • Susan Clawson
Regular Paper

Abstract

Paraneoplastic cerebellar degeneration accompanying gynecological or breast malignancies is frequently associated with an autoantibody response, termed “type I” or “anti-Yo” directed against cytoplasmic antigens of cerebellar Purkinje cells. The role of this antibody response in the pathogenesis of paraneoplastic cerebellar degeneration is unknown; however, it is also not known whether anti-Purkinje cell antibodies from the systemic circulation bind to target Purkinje cell antigens under the conditions of brain inflammation and blood-brain barrier disruption, which are frequently present at the onset of cerebellar symptoms. Inbred Lewis rats received intraperitoneal injections of type I or normal IgG in the setting of blood-brain barrier disruption induced by adoptive transfer of experimental allergic encephalomyelitis (EAE) and were killed after 24, 48, and 96h. Brains of these animals were studied histologically for evidence of EAE and immunohistochemically for binding of human or endogenous rat IgG to target neurons. Rat IgG was detected around vessels and in Purkinje cells of all animals studied. Human IgG was detected around vessels of all animals. In animals examined 96 h after receiving type I human IgG, human IgG was identified within processes of Purkinje cells and within occasional Purkinje cell bodies. Uptake of type I IgG by other cell types was not observed, and neuronal uptake of IgG was not seen in brains of animals receiving normal human IgG. Our data demonstrate that circulating type I IgG is internalized by cerebellar Purkinje cells in the setting of blood-brain barrier disruption and suggest a mechanism by which an antibody response directed against cytoplasmic antigens of Purkinje cells may reach target antigens at the onset of paraneoplastic cerebellar degeneration.

Key words

Purkinje cells Blood-brain barrier Human anticerebellar antibody Rat Paraneoplastic syndromes 

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References

  1. 1.
    Anderson NE, Rosenblum MK, Posner JB (1988) Paraneoplastic cerebellar degeneration: clinical immunological correlations. Ann Neurol 24: 559–567Google Scholar
  2. 2.
    Borges LF, Busis NA (1985) Intraneuronal accumulation of myeloma proteins. Arch Neurol 42: 690–695Google Scholar
  3. 3.
    Borges LF, Elliott PJ, Gill R, Iversen SD, Iversen LL (1985) Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinie neurons. Science 228:346–348Google Scholar
  4. 4.
    Brain L, Wilkinson M (1965) Subacute cerebellar degeneration associated with neoplasms. Brain 88: 465–478Google Scholar
  5. 5.
    Brashear HR, Greenlee JE, Jaeckle KA, Rose JW (1989) Anticerebellar antibodies in neurologically normal patients with ovarian neoplasms. Neurology 39: 1605–1609Google Scholar
  6. 6.
    Burns J, Rosenzweig A, Zweiman B, Moskovitz A, Lisak R (1984) Recovery of myelin basic protein reactive T cells from spinal cords of lewis rats with autoimmune encephalomyelitis. J Immunol 132: 2690–2692Google Scholar
  7. 7.
    Cunningham J, Graus F, Anderson N, Posner JB (1986) Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration. Neurology 36: 1163–1168Google Scholar
  8. 8.
    Fabian RH, Petroff G (1987) Intraneuronal IgG in the central nervous system: uptake by retrograde transport. Neurology 37: 1780–1784Google Scholar
  9. 9.
    Furneaux HM, Reich L, Posner JB (1990) Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 40: 1085–1091Google Scholar
  10. 10.
    Furneaux HM, Rosenblum MK, Dalmau J, Wong E, Woodruff P, Graus F, Posner JB (1990) Selective expression of Purkinje cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration. N Engl J Med 322: 1844–1851Google Scholar
  11. 11.
    Graus F, Seguardo OG, Tolosa E (1988) Selective concentration of anti-Purkinje cell antibody in the CSF of two patients with paraneoplastic cerebellar degeneration. Acta Neurol Scand 78: 210–213Google Scholar
  12. 12.
    Graus F, Illa I, Agusta M, Ribalta T, Cruz-Sanchez F, Juarez C (1991) Effect of intraventricular injection of anti-Purkinje cell antibody (anti-Yo) in a guinea pig model. J Neurol Sci 106: 82–87Google Scholar
  13. 13.
    Greenlee JE, Brashear HR (1983) Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol 14: 609–613Google Scholar
  14. 14.
    Greenlee JE, Lipton HK (1986) Anticerebellar antibodies in serum and cerebrospinal fluid of a patient with oat cell carcinoma of the lung and paraneoplastic cerebellar degeneration. Ann Neurol 19: 82–85Google Scholar
  15. 15.
    Greenlee JE, Brashear HR, Herndon RM (1988) Immunoperoxidase labeling of rat brain sections with sera from patients with paraneoplastic cerebellar degeneration and systemic neoplasia. J Neuropathol Exp Neurol 47: 561–571Google Scholar
  16. 16.
    Greenlee JE, Parks TN, Jaeckle KA (1993) Type IIa (“anti-Hu”) antineuronal antibodies produce destruction of rat cerebellar granule neurons in vitro. Neurology 43: 2049–2054Google Scholar
  17. 17.
    Henson RA, Urich H (1982) Cortical cerebellar degeneration. In: Henson RA, Urich H (eds) Cancer and the nervous system: the neurological manifestations of systemic malignant disease. Blackwell, Oxford, pp 346–367Google Scholar
  18. 18.
    Hirano A, Dembitzer HM, Becker NH, Levine S, Zimmerman HM (1970) Fine structural alterations in the blood-brain barrier in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 29: 432–440Google Scholar
  19. 19.
    Jaeckle KA, Graus F, Houghton A, Cordon-Cardo C, Nielsen SL, Posner JB (1985) Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic antigen. Ann Neurol 18: 592–600Google Scholar
  20. 20.
    Jaeckle KA, Stroop WG, Greenlee JE, Price M, Deng QS (1986) Intraventricular injection of paraneoplastic anti-Purkinje cell antibody in a rat model. Neurology 36: 332Google Scholar
  21. 21.
    Lampert P, Carpenter S (1965) Electron microscopic studies on the vascular permeability and the mechanism of demyelination in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 24: 11–24Google Scholar
  22. 22.
    Linington C, Bradl M, Lassmann H, Brunner C, Vass K (1988) Augmentation of demyelination in rat acute alleric encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 130: 443–454Google Scholar
  23. 23.
    Oldstone MBA, Dixon FJ (1968) Immunohistochemical study of allergic encephalomyelitis. Am J Pathol 52: 251–257Google Scholar
  24. 24.
    Rodriguez M, Truh LI, O'Neill BP, Lennon VA (1988) Autoimmune paraneoplastic cerebellar degeneration: ultrastructural localization of antibody-binding sites in Purkinje cells. Neurology 38: 1380–1386Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • John E. Greenlee
    • 1
    • 2
  • James B. Burns
    • 1
    • 2
  • J. W. Rose
    • 1
    • 2
  • Kurt A. Jaeckle
    • 1
    • 2
  • Susan Clawson
    • 1
    • 2
  1. 1.Neurology Service (127)Veterans Affairs Medical CenterSalt Lake CityUSA
  2. 2.Department of NeurologyUniversity of Utah School of MedicineSalt Lake CityUSA

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