Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK
| العنوان: | Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK |
|---|---|
| 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) |
| بيانات النشر: | Public Library of Science, 2015. |
| سنة النشر: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1875a70e7cb11c750cc4c1b6337a0a7Test http://europepmc.org/articles/PMC4403992Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f1875a70e7cb11c750cc4c1b6337a0a7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|