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Article Dans Une Revue Blood Année : 2007

The thymic theme of acetylcholinesterase splice variants in myasthenia gravis

Paul Lacoste
  • Fonction : Auteur
Lilach Soreq
  • Fonction : Auteur
Geraldine Cizeron-Clairac
  • Fonction : Auteur
Rozen Le Panse
Frederique Truffault
  • Fonction : Auteur
Iftach Shaked
  • Fonction : Auteur
Hermona Soreq
  • Fonction : Auteur
Sonia Berrih-Aknin

Résumé

Abstract 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-βII. 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.

Dates et versions

hal-03442090 , version 1 (22-11-2021)

Identifiants

Citer

Adi Gilboa-Geffen, Paul Lacoste, Lilach Soreq, Geraldine Cizeron-Clairac, Rozen Le Panse, et al.. The thymic theme of acetylcholinesterase splice variants in myasthenia gravis. Blood, 2007, 109 (10), pp.4383-4391. ⟨10.1182/blood-2006-07-033373⟩. ⟨hal-03442090⟩
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