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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4383-4391. Prepublished online as a Blood First Edition Paper on February 1, 2007; DOI 10.1182/blood-2006-07-033373. This Article Full Text Full Text (PDF) Supplemental Figure and Tables All Versions of this Article: blood-2006-07-033373v1 109/10/4383    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gilboa-Geffen, A. Articles by Berrih-Aknin, S. Search for Related Content PubMed PubMed Citation Articles by Gilboa-Geffen, A. Articles by Berrih-Aknin, S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The thymic theme of acetylcholinesterase splice variants in myasthenia gravis Adi Gilboa-Geffen1, Paul P. Lacoste2, Lilach Soreq1, Geraldine Cizeron-Clairac2, Rozen Le Panse1, Frederique Truffault2, Iftach Shaked1, Hermona Soreq1, and Sonia Berrih-Aknin2 1 Hebrew University of Jerusalem, Israel; 2 Centre National de la Recherche Scientifique–Unité Mixte de Recherche (CNRS-UMR) 8162, Institut Paris-Sud Cytokines (IPSC), Université Paris XI, Hôpital Marie Lannelongue, Le Plessis Robinson, France Cholinergic signaling and acetylcholinesterase (AChE) influence immune response and inflammation. Autoimmune myasthenia gravis (MG) is mediated by antibodies to the acetylcholine receptor and current therapy is based on anti-AChE drugs. MG is associated with thymic hyperplasia, showing signs of inflammation. The objectives of this study were to analyze the involvement of AChE variants in thymic hyperplasia. We found lower hydrolytic activities in the MG thymus compared with adult controls, accompanied by translocation of AChE-R from the cytoplasm to the membrane and increased expression of the signaling protein kinase PKC-ßII. To explore possible causal association of AChE-R changes with thymic composition and function, we used an AChE-R transgenic model and showed smaller thymic medulla compared with strain-matched controls, indicating that AChE-R overexpression interferes with thymic differentiation mechanisms. Interestingly, AChE-R transgenic mice showed increased numbers of CD4+CD8+ cells that were considerably more resistant in vitro to apoptosis than normal thymocytes, suggesting possibly altered positive selection. We further analyzed microarray data of MG thymic hyperplasia compared with healthy controls and found continuous and discrete changes in AChE-annotated GO categories. Together, these findings show that modified AChE gene expression and properties are causally involved in thymic function and development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Berson, M. Knobloch, M. Hanan, S. Diamant, M. Sharoni, D. Schuppli, B. C. Geyer, R. Ravid, T. S. Mor, R. M. Nitsch, et al. Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology Brain, January 1, 2008; 131(1): 109 - 119. [Abstract] [Full Text] [PDF]

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