Skip Navigation



Brain Advance Access published online on October 11, 2005
Brain, doi:10.1093/brain/awh625
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
128/11/2665    most recent
awh625v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Orr, C. F.
Right arrow Articles by Halliday, G. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Orr, C. F.
Right arrow Articles by Halliday, G. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 3, 2004
Revised July 30, 2005
Accepted August 1, 2005

Article

A possible role for humoral immunity in the pathogenesis of Parkinson's disease

Carolyn F. Orr 1, Dominic B. Rowe 2, Yoshikuni Mizuno 3, Hideo Mori 3, and Glenda M. Halliday 1*

1 Prince of Wales Medical Research Institute, University of New South Wales, Randwick, NSW, Australia
2 Department of Neurology, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia
3 Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan

* To whom correspondence should be addressed.
Glenda M. Halliday, E-mail: g.halliday{at}unsw.edu.au


  Abstract

The pathogenesis of idiopathic Parkinson's disease is unknown, but nigral degeneration and depigmentation are associated with microglial inflammation and anti-inflammatory medications appear to protect against the disease. The possibility that humoral immunity may play a role in initiating or regulating the inflammation has been suggested by experimental studies triggering dopamine cell death using a variety of transfer strategies and the observation of CD8+ T lymphocytes and complement in the nigra in Parkinson's disease. We analysed the association between degeneration and humoral immune markers in brain tissue of patients with idiopathic (n = 13) or genetic (n = 2 with {alpha}-synuclein and n = 1 with parkin mutations) Parkinson's disease and controls without neurological disease (n = 12) to determine the humoral immune involvement in Parkinson's disease. Formalin-fixed tissue samples from the substantia nigra and primary visual cortex for comparison were stained for {alpha}-synuclein, major histocompatibility complex II (HLA), immunoglobulin M (IgM), immunoglobulin G (IgG), IgG subclasses 1-4 and IgG receptors Fc{gamma}R I-III. Antigen retrieval and both single immunoperoxidase and double immunofluorescence procedures were employed to determine the cell types involved and their pattern and semiquantitative densities. Significant dopamine neuron loss occurred in all patients with Parkinson's disease, negatively correlating with disease duration (r = -0.76, P = 0.002). Although all patients had increased inflammatory HLA immunopositive microglia, the degree of inflammation was similar throughout the disease (r = 0.08, P = 0.82). All patients with Parkinson's disease had IgG binding on dopamine neurons but not IgM binding. Lewy bodies were strongly immunolabelled with IgG. A mean 30 ± 12% of dopamine nigral neurons were immunoreactive for IgG in Parkinson's disease with the proportion of IgG immunopositive neurons negatively correlating with the degree of cell loss in the substantia nigra (r = -0.67, P < 0.0001) and positively correlating with the number of HLA immunopositive microglia (r = 0.51, P = 0.01). Most neuronal IgG was the IgG1 subclass with some IgG3 and less IgG2 also found in the damaged substantia nigra. The high affinity activating IgG receptor, Fc{gamma}RI, was expressed on nearby activated microglia. The low affinity activating IgG receptor, Fc{gamma}RIII was expressed on cells morphologically resembling lymphocytes, whereas immunoreactivity for the inhibitory IgG receptor Fc{gamma}RII was absent in all cases. This pattern of humoral immune reactivity is consistent with an immune activation of microglia leading to the targeting of dopamine nigral neurons for destruction in both idiopathic and genetic cases of Parkinson's disease.

Keywords: Parkinson's disease; microglia; humoral immunity; neuropathology.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
A. D. Reynolds, R. Banerjee, J. Liu, H. E. Gendelman, and R. L. Mosley
Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease
J. Leukoc. Biol., November 1, 2007; 82(5): 1083 - 1094.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
V. Rigau, M. Morin, M.-C. Rousset, F. de Bock, A. Lebrun, P. Coubes, M.-C. Picot, M. Baldy-Moulinier, J. Bockaert, A. Crespel, et al.
Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy
Brain, July 1, 2007; 130(7): 1942 - 1956.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.