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BioDrugs

, Volume 15, Issue 6, pp 351–355 | Cite as

Does Parkinson’s Disease Have an Immunological Basis?

The Evidence and its Therapeutic Implications
  • Urszula Fiszer
Leading Article

Abstract

Parkinson’s disease (PD) is an age-related neurodegenerative movement disorder of unknown aetiology. Immune abnormalities have been described in PD including the occurrence of autoantibodies against neuronal structures and high numbers of microglia cells expressing the histocompatibility glycoprotein human leucocyte antigen-DR in the substantia nigra. An infectious cause for PD has been discussed for years. Disturbed cellular and humoral immune functions in peripheral blood of patients with PD have been also reported. An elevated γδ+ T cell population and increased immunoglobulin G immunity in CSF to heat shock proteins have been found in PD. Cytokines and apoptosis-related proteins were elevated in the striatum in patients with PD. Activated glial cells may participate in neuronal cell death in PD by providing toxic substances. We may conclude that the immune system is involved in the pathogenesis of PD. However, we are not able to determine whether the disturbances described above constitute a primary or secondary phenomenon. Immunomodulatory agents may have important applications in the development of new therapies for PD.

Keywords

Substantia Nigra Lewy Body Human Leucocyte Antigen Bordetella Pertussis Immune Abnormality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Supported in part by a grant from the Medical Center for Postgraduate Education in Warsaw, Poland.

References

  1. 1.
    Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 1999; 22: 123–44PubMedCrossRefGoogle Scholar
  2. 2.
    Müller U, Graeber MB, Haberhausen G, et al. Molecular basis and diagnosis of neurogenetic disorders. J Neurol Sci 1994; 124: 119–40PubMedCrossRefGoogle Scholar
  3. 3.
    Kuhn W, Müller T, Nastos I, et al. The neuroimmune hypothesis in Parkinson’s disease. Rev Neurosci 1997; 8: 29–34PubMedGoogle Scholar
  4. 4.
    Pouplard A, Emile J, Pouplard F, et al. Parkinsonism and auto-immunity: antibody against human sympathetic ganglion cells in Parkinson’s disease. Adv Neurol 1979; 24: 321–6Google Scholar
  5. 5.
    McRae-Degueurce A, Rosengren L, Haglid K, et al. Immuno-cytochemical investigations on the presence of neuronspecific antibodies in the CSF of Parkinson disease cases. Neurochem Res 1988; 13: 679–84PubMedCrossRefGoogle Scholar
  6. 6.
    Chen S, Le WD, Xie WJ, et al. Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. Arch Neurol 1998; 55: 1075–80PubMedCrossRefGoogle Scholar
  7. 7.
    Marttila RJ, Eskola J, Päivärinta M, et al. Immune functions in Parkinson’s disease. Adv Neurol 1984; 40: 315–23PubMedGoogle Scholar
  8. 8.
    Fiszer U, Piotrowska K, Korlak J, et al. The immunological status in Parkinson’s disease. Med Lab Sci 1991;48: 196–200PubMedGoogle Scholar
  9. 9.
    Fiszer U, Mix E, Fredrikson S, et al. V region T cell receptor repertoire in Parkinson’s disease. Acta Neurol Scand 1996; 93: 25–9PubMedCrossRefGoogle Scholar
  10. 10.
    Fiszer U, Mix E, Fredrikson S, et al. Parkinson’s disease and immunological abnormalities: increase of HLA-DR expression on monocytes in cerebrospinal fluid and of CD45RO+ T cells in peripheral blood. Acta Neurol Scand 1994; 90: 160–6PubMedCrossRefGoogle Scholar
  11. 11.
    Marttila RJ, Eskola J, Soppi E, et al. Immune functions in Parkinson’s diseases. Lymphocyte subsets, concanavalin A induced suppressor cell activity and in vitro immunoglobulin production. J Neurol Sci 1985; 69: 121–34PubMedCrossRefGoogle Scholar
  12. 12.
    Yamada T, Akiyama M, McGeer PL. Complement activated oligodendroglia: a new pathogenic entity identified by immunostaining with antibodies to human complement proteins C3d and C4d. Neurosci Lett 1990; 112: 161–6PubMedCrossRefGoogle Scholar
  13. 13.
    McGeer PL, Itagaki S, Boyes BE, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988;38: 1285–91PubMedCrossRefGoogle Scholar
  14. 14.
    Hickey WF, Hsu BL, Kimura H. T-lymphocyte entry into the central nervous system. J Neurosci Res 1991; 28: 254–60PubMedCrossRefGoogle Scholar
  15. 15.
    Mogi M, Harada H, Riederer P, et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 1994; 165:1–2, 208–10PubMedCrossRefGoogle Scholar
  16. 16.
    Mogi M, Harada H, Narabayashi H, et al. Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson’s disease. Neurosci Lett 1996; 211:1, 13–6PubMedCrossRefGoogle Scholar
  17. 17.
    Blum-Degen D, Müller TH, Kuhn W, et al. Interleukin-1-beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett 1995; 202: 17–20PubMedCrossRefGoogle Scholar
  18. 18.
    Fiszer U, Mix E, Fredrikson S, et al. γδ+T cells are increased in patients with Parkinson’s disease. J Neurol Sci 1994; 121: 39–45PubMedCrossRefGoogle Scholar
  19. 19.
    O’Brien RL, Born W. Heat shock proteins as antigens for γδ T cells. Semin Immunol 1991; 3: 81–7PubMedGoogle Scholar
  20. 20.
    Kaufmann SHE. Heat shock proteins and the immune response. Immunol Today 1990; 11: 129–36PubMedCrossRefGoogle Scholar
  21. 21.
    Gao YL, Raine CS, Brosnan C. Humoral response to hsp 65 in multiple sclerosis and other neurological conditions. Neurology 1994; 44: 941–6PubMedCrossRefGoogle Scholar
  22. 22.
    Fiszer U, Fredrikson S, Czonkowska A. Humoral response to hsp 65 and hsp 70 in cerebrospinal fluid in Parkinson’s disease. J Neurol Sci 1996; 139: 66–70PubMedCrossRefGoogle Scholar
  23. 23.
    Chopp M. The roles of heat shock proteins and immediate early genes in central nervous system normal function and pathology. Curr Opin Neurol Neurosurg 1993; 6: 6–10PubMedGoogle Scholar
  24. 24.
    Craig EA, Gambill BB, Nelson RJ. Heat shock proteins: molecular chaperones of protein biogenesis. Microbiol Rev 1993; 57:402–14PubMedGoogle Scholar
  25. 25.
    Lakey EK, Margoliash E, Pierce SK. Identification of a peptide binding protein that plays a role in antigen presentation. Proc Natl Acad Sci USA 1987; 84: 1659–63PubMedCrossRefGoogle Scholar
  26. 26.
    Manara GC, Sansoni P, Badiali De Giorgi L, et al. New insights suggesting a possible role of a heat shock protein 70kD family related protein in antigen processing/presentation phenomenon in humans. Blood 1993; 82: 2865–71PubMedGoogle Scholar
  27. 27.
    Jellinger KA. Cytoskeletal pathology in parkinsonism and aging brain. In: Calne PB, Comi B, Crippo D, et al., editors. Park aging. New York: Raven Press, 1989: 35–56Google Scholar
  28. 28.
    Elizan TS, Schwartz J, Yahr MD, et al. Antibodies against arboviruses in postencephalitic and idiopathic Parkinson’s disease. Arch Neurol 1978; 35: 257–60PubMedCrossRefGoogle Scholar
  29. 29.
    Takahashi M, Yamada T. Viral etiology for Parkinson’s disease — a possible role of influenza A virus infection. Jpn J Infect Dis 1999; 52(3): 89–98PubMedGoogle Scholar
  30. 30.
    Martilla RJ, Arstila P, Nikoskelaimen J. Viral antibodies in the sera from patients with Parkinson’s disease. Eur Neurol 1977; 15: 25–33CrossRefGoogle Scholar
  31. 31.
    Kohbata S, Beaman BL. L-DOPA-responsive movement disorder caused by Nocardia asteroides localized in the brains of mice. Infect Immune 1991; 59: 181–91Google Scholar
  32. 32.
    de Pedro-Cuesta J, Gudmundsson G, Abraira V, et al. Whooping cough and Parkinson’s disease. The Europarkinson Preparatory Activity Research Group. Int J Epidemiol 1996; 25(6): 1301–11PubMedCrossRefGoogle Scholar
  33. 33.
    Jellinger KA. Cell death mechanisms in Parkinson’s disease. J Neural Transm 2000; 107: 1–29PubMedCrossRefGoogle Scholar
  34. 34.
    Blum D, Wu Y, Nissou MF, et al. p53 and Bax activation in 6-hydroxydopamine-induced apoptosis in PC12 cells. Brain Res 1997; 751: 139–42PubMedCrossRefGoogle Scholar
  35. 35.
    Tatton NA, Kish SJ. In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxy-nucleotidyl transferase labelling and acidine orange staining. Neuroscience 1997; 77: 1037–48PubMedCrossRefGoogle Scholar
  36. 36.
    Mogi M, Nagatsu T. Neurotrophins and cytokines in Parkinson’s disease. In: Stern GM, editor. Parkinson’s disease. Adv Neurol vol. 80. Philadelphia: Lippincott Williams & Wilkins, 1999: 135–40Google Scholar
  37. 37.
    de la Monte SM, Son YK, Ganju N, et al. p53- and CD95-associated apoptosis in neurodegenerative diseases. Lab Invest 1998; 78: 401–11PubMedGoogle Scholar
  38. 38.
    Mogi M, Togari A, Kondo T, et al. Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from Parkinsonian brain. J Neural Transm 2000; 17: 335–41CrossRefGoogle Scholar
  39. 39.
    Hunot S, Bragg B, Ricard D, et al. Nuclear translocation of NF-kappa-B is increased in dopaminergic neurons of patients with Parkinson’s diseases. Proc Natl Acad Sci USA 1997; 94: 7531–6PubMedCrossRefGoogle Scholar
  40. 40.
    Bok G, Anglade P, Wallach D, et al. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s diseases. Neurosci Lett 1994; 172:1–2, 151–4CrossRefGoogle Scholar
  41. 41.
    Hunot S, Dugas N, Faucheux B, et al. FcepsilonRII/CD23 is expressed in Parkinson’s diseases and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 1999; 19(9): 3440–7PubMedGoogle Scholar
  42. 42.
    Hirsch EC. Glial cells and Parkinson’s disease. J Neurol 2000; 247Suppl. 2:II58–62PubMedCrossRefGoogle Scholar
  43. 43.
    Hunat S, Boissiere F, Faucheux B, et al. Nitric oxidase synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience 1996; 72: 355–63CrossRefGoogle Scholar
  44. 44.
    Krüger R, Hardt C, Tschentscer F, et al. Genetic analysis of immunomodulating factors in sporadic Parkinson’s disease. J Neural Transm 2000; 107: 553–62PubMedCrossRefGoogle Scholar
  45. 45.
    Cross RJ, Brooks WH, Roszman TL, et al. Hypothalamic immune interaction. Effect of hypophysectomy on neuroimmunoregulation. J Neurol Sci 1982; 53: 557–66PubMedCrossRefGoogle Scholar
  46. 46.
    Newsom-Davis J, Vincent A. Receptors, antibodies and disease. Immunol Today 1982; 3: 149–51CrossRefGoogle Scholar
  47. 47.
    Dunnett SB, Björklun A. Prospects for new restorative and neuroprotective treatment in Parkinson’s disease. Nature 1999; 399: A32–9PubMedCrossRefGoogle Scholar
  48. 48.
    Ziv I, Melamed E. Role of apoptosis in the pathogenesis of Parkinson’s disease: a novel therapeutic opportunity? Move Disord 1998; 13(6): 865–70CrossRefGoogle Scholar
  49. 49.
    Selmaj K, Raine CS, Cross AH. Anti-tumor necrosis factortherapy abrogates autoimmune demyelination. Ann Neurol 1991; 30(5): 694–700PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Urszula Fiszer
    • 1
  1. 1.Department of Neurology and EpileptologyMedical Center for Postgraduate EducationWarsawPoland

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