The chemokine CXCL13 is a key molecule in autoimmune myasthenia gravis
| Autor: | Rozen Le Panse, Géraldine Cizeron-Clairac, Chantal Tallaksen, Frédérique Truffault, Amel Meraouna, Jacky Bismuth, Sonia Berrih-Aknin |
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| Přispěvatelé: | CNRS-UMR 8162, Institut Paris-Sud Cytokines (IPSC), Université Paris XI, Hopital Marie Lannelongue, Le Plessis-Robinson, France, Department of Neurology, Ulleval University Hospital, Oslo, Norway, Institut Paris-sud cytokines (IPSC), Université Paris-Sud - Paris 11 (UP11)-Centre Chirurgical Marie Lannelongue (CCML)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Adult
Chemokine medicine.medical_treatment Immunology Thymus Gland Biology Biochemistry Pathogenesis 03 medical and health sciences 0302 clinical medicine Adrenal Cortex Hormones Myasthenia Gravis medicine Humans CXCL13 ComputingMilieux_MISCELLANEOUS 030304 developmental biology Oligonucleotide Array Sequence Analysis Chemokines Cytokines and Interleukins 0303 health sciences Gene Expression Profiling Germinal center Chemotaxis Epithelial Cells Cell Biology Hematology medicine.disease Germinal Center Chemokine CXCL13 Myasthenia gravis 3. Good health Thymectomy Gene Expression Regulation Case-Control Studies biology.protein [SDV.IMM]Life Sciences [q-bio]/Immunology Female Antibody Chemokines CXC 030217 neurology & neurosurgery |
| Zdroj: | Blood Blood, American Society of Hematology, 2006, 108 (2), pp.432-440. ⟨10.1182/blood-2005-06-2383⟩ Blood, 2006, 108 (2), pp.432-440. ⟨10.1182/blood-2005-06-2383⟩ |
| ISSN: | 0006-4971 1528-0020 |
| Popis: | Myasthenia gravis (MG) is associated with ectopic germinal centers in the thymus. Thymectomy and glucocorticoids are the main treatments but they induce operative risks and side effects, respectively. The aim of this study was to propose new therapies more efficient for MG. We hypothesized that molecules dysregulated in MG thymus and normalized by glucocorticoids may play a key role in thymic pathogenesis. Using gene chip analysis, we identified 88 genes complying with these criteria, the most remarkable being the B-cell chemoattractant (CXCL13). Its expression was increased in thymus and sera of glucocorticoid-untreated patients and decreased in response to treatment in correlation with clinical improvement. Normal B cells were actively chemoattracted by thymic extracts from glucocorticoid-untreated patients, an effect inhibited by anti-CXCL13 antibodies. In the thymus, CXCL13 was preferentially produced by epithelial cells and overproduced by epithelial cells from MG patients. Altogether, our results suggest that a high CXCL13 production by epithelial cells could be responsible for germinal center formation in MG thymus. Furthermore, they show that this gene is a main target of corticotherapy. Thus, new therapies targeting CXCL13 could be of interest for MG and other autoimmune diseases characterized by ectopic germinal center formation. |
| Databáze: | OpenAIRE |
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