المؤلفون: Vuslat Yilmaz, Piraye Oflazer, Fikret Aysal, Hacer Durmus, Kostas Poulas, Sibel P Yentur, Yesim Gulsen-Parman, Socrates Tzartos, Alexander Marx, Erdem Tuzun, Feza Deymeer, Güher Saruhan-Direskeneli

المصدر: PLoS ONE, Vol 10, Iss 4, p e0123546 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/0de3ce75fb9243d1834b5949a1492d14Test

المؤلفون: Konstantinos Lazaridis, Socrates J. Tzartos, Panagiota Evangelakou, George Lagoumintzis, Paraskevi Zisimopoulou, Labrini Skriapa, Eirini Grapsa, Ioannis Kanelopoulos, Kostas Poulas, Nikos Trakas

المصدر: Annals of the New York Academy of Sciences. 1275:7-12

مصطلحات موضوعية: 0303 health sciences, biology, Chemistry, General Neuroscience, Autoantibody, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Neuromuscular junction, Myasthenia gravis, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, History and Philosophy of Science, Toxicity, Immunology, medicine, Extracellular, biology.protein, Animal studies, Antibody, 030217 neurology & neurosurgery, 030304 developmental biology, Acetylcholine receptor

الوصف: Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction, usually caused by autoantibodies against the acetylcholine receptor (AChR) or the muscle-specific kinase (MuSK). Our aim is the development of a therapy based on the selective extracorporeal elimination of anti-AChR or anti-MuSK antibodies. To this end, the extracellular domains of the AChR subunits and MuSK have been expressed in yeast to be used as adsorbents, after optimization, and to obtain large quantities of proteins with near-native structure. We have characterized these proteins with respect to their use as specific immunoadsorbents for MG autoantibodies, and have begun large-scale experiments in order to verify the feasibility of application of the method for therapy. Furthermore, we have initiated animal studies to test possible toxicity and safety issues of the adsorbents or the procedure itself. The successful completion of the scale-up and safety tests will allow the initiation of clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e42901765d9790fe63c4ab0b78912c01Test
https://doi.org/10.1111/j.1749-6632.2012.06788.xTest

المؤلفون: Feza Deymeer, Kostas Poulas, Yesim Gulsen-Parman, Piraye Oflazer, Hacer Durmus, Erdem Tüzün, Fikret Aysal, Alexander Marx, Vuslat Yilmaz, Güher Saruhan-Direskeneli, Sibel P. Yentür, Socrates J. Tzartos

المصدر: PLoS ONE
PLoS ONE, Vol 10, Iss 4, p e0123546 (2015)

مصطلحات موضوعية: Adult, CD4-Positive T-Lymphocytes, Male, medicine.medical_specialty, CD3 Complex, Science, medicine.medical_treatment, CD40 Ligand, Neuromuscular transmission, Cell Separation, Peripheral blood mononuclear cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, Myasthenia Gravis, medicine, Humans, Receptors, Cholinergic, RNA, Messenger, Receptor, Autoantibodies, Demography, Immunosuppression Therapy, Multidisciplinary, CD40, biology, Interleukin-12 Subunit p40, Receptor Protein-Tyrosine Kinases, medicine.disease, Myasthenia gravis, 3. Good health, Endocrinology, Cytokine, Immunology, biology.protein, Leukocytes, Mononuclear, Medicine, Cytokines, Female, Antibody, 030217 neurology & neurosurgery, 030215 immunology, Research Article

الوصف: Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4(+) T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-gamma, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-. and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1875a70e7cb11c750cc4c1b6337a0a7Test
http://europepmc.org/articles/PMC4403992Test

المؤلفون: Konstantinos, Lazaridis, Paraskevi, Zisimopoulou, George, Lagoumintzis, Labrini, Skriapa, Nikos, Trakas, Panagiota, Evangelakou, Ioannis, Kanelopoulos, Eirini, Grapsa, Kostas, Poulas, Socrates, Tzartos

المصدر: Annals of the New York Academy of Sciences. 1275

مصطلحات موضوعية: Myasthenia Gravis, Blood Component Removal, Humans, Receptors, Cholinergic, Immunosorbents, Autoantigens, Autoantibodies

الوصف: Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction, usually caused by autoantibodies against the acetylcholine receptor (AChR) or the muscle-specific kinase (MuSK). Our aim is the development of a therapy based on the selective extracorporeal elimination of anti-AChR or anti-MuSK antibodies. To this end, the extracellular domains of the AChR subunits and MuSK have been expressed in yeast to be used as adsorbents, after optimization, and to obtain large quantities of proteins with near-native structure. We have characterized these proteins with respect to their use as specific immunoadsorbents for MG autoantibodies, and have begun large-scale experiments in order to verify the feasibility of application of the method for therapy. Furthermore, we have initiated animal studies to test possible toxicity and safety issues of the adsorbents or the procedure itself. The successful completion of the scale-up and safety tests will allow the initiation of clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::8b7c3c6127dc28d8ac94638afddb680dTest
https://pubmed.ncbi.nlm.nih.gov/23278571Test