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Naazneen Ibtehaj, Karl E Anderson, Ruksana Huda
We investigated potential therapeutic effects of a conjugate of BAFF receptor specific- monoclonal antibody and short interference RNA in a mouse model of myasthenia gravis (EAMG). Whereas high-dose siRNA conjugate resulted in significant accumulation of Fas expressing CD19+/ B220+ cells and concurrent expression of type 1 interferon in lymph nodes, low-dose conjugate did not induce FAS expression but caused marked BAFF receptor deficiency in lymph nodes that was further associated with improved MG symptoms...
January 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Konstantinos Lazaridis, Vassiliki Baltatzidi, Nikolaos Trakas, Eleni Koutroumpi, Nikolaos Karandreas, Socrates J Tzartos
Myasthenia gravis (MG) is usually caused by antibodies against the muscle acetylcholine receptor (AChR). Experimental autoimmune MG (EAMG) is the animal model of MG, typically induced by immunization of rodents with AChR isolated from the electric organ of Torpedo californica. We have successfully induced EAMG in Lewis rats by immunization with the extracellular domains (ECDs) of the human AChR subunits (α, β, γ, δ and ε) expressed in yeast. Analysis of the antibody titers revealed a robust antigenic response against all the peptides, but a marked difference in their pathogenicity; the α subunit ECD was the most pathogenic, resulting in the highest percentage of affected animals...
December 21, 2016: Journal of Neuroimmunology
Henry J Kaminski, Keiichi Himuro, Jumana Alshaikh, Bendi Gong, Georgiana Cheng, Linda L Kusner
The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM...
2016: Frontiers in Physiology
Yingguo Ren, Baochao Zhang, Dongpei Jia, Ke Hu
Objective To investigate the effects of tetramethylpyrazine (TMP) on experimental autoimmune myasthenia gravis (EAMG) in rats and explore the possible immune regulation mechanism. Methods Lewis rats were randomly divided into 4 groups: control group, EAMG group, TMP low-dose group (TMP-L, 10 mg/kg) and TMP high-dose group (TMP-H, 20 mg/kg). Except the control group, the other 3 groups were subjected to EAMG modeling. The body mass was determined and the symptoms of muscular weakness in rats were scored by Lennon EAMG criteria...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Qing-Fang Meng, Zheng Zhang, Yan-Jun Wang, Wei Chen, Fei-Fei Li, Long-Tao Yue, Chang-Jun Zhang, Heng Li, Min Zhang, Cong-Cong Wang, Peng Zhang, Hui Chen, Rui-Sheng Duan, Shan-Mei Sun, Yan-Bin Li
Astilbin, a major bioactive compound extracted from Rhizoma smilacis glabrae (RSG), has been reported to possess immunosuppressive properties. Our study first evaluated the effect of astilbin on experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. The results showed that astilbin could attenuate the severity of EAMG by decreasing antigen-specific autoantibodies with up-regulation of regulatory T cells and down-regulation of Th17 cells. In addition to, astilbin also reduced the efficiency of the antigen presenting cells on which the expression of MHC class II decreased...
September 15, 2016: Journal of Neuroimmunology
Wei Chen, Qing-Fang Meng, Jun-Kang Sui, Yan-Jun Wang, Xiao-Li Li, Shen Liu, Heng Li, Cong-Cong Wang, Chun-Hong Li, Yan-Bin Li
Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by fatigue and muscle weakness. Ginseng is used in the treatment of MG. Ginsenoside Rb1 (G-Rb1), the most abundant ginsenoside in ginseng root, has been proved to be immune regulatory in various diseases. In this study, we investigated the effects and mechanisms of G-Rb1 in treatment for MG in a rat model. Our data showed that G-Rb1 treatment markedly ameliorated the symptoms of experimental autoimmune myasthenia gravis (EAMG) rats, decreased the percentage of Th17 cells in mononuclear cells (MNCs), and increased the number of Treg and Th2 cells in MNCs...
December 2016: International Immunopharmacology
Jian Rong Sheng, Kourosh Rezania, Betty Soliven
Regulatory B cells (Bregs) attenuate the severity of experimental autoimmune myasthenia gravis (EAMG) in an interleukin-10 (IL-10)-dependent manner. The goal of this study was to investigate the role of human Bregs in MG focusing on CD19(+)CD1d(hi) CD5(+) and CD19(+)CD24(hi)CD38(hi) subsets. We found that MG patients exhibited a decrease in the frequency of both Breg subsets and IL-10 producing B cells within each subset, which correlated with disease severity. In addition, there was impaired suppression of Th1 polarization in MG...
August 15, 2016: Journal of Neuroimmunology
Melike Küçükerden, Ruksana Huda, Erdem Tüzün, Abdullah Yılmaz, Lamprini Skriapa, Nikos Trakas, Richard T Strait, Fred D Finkelman, Sevil Kabadayı, Paraskevi Zisimopoulou, Socrates Tzartos, Premkumar Christadoss
Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice...
June 15, 2016: Journal of Neuroimmunology
Marieke Robinet, Solène Maillard, Mélanie A Cron, Sonia Berrih-Aknin, Rozen Le Panse
Abnormal toll-like receptor (TLR) activation and uncontrolled resolution of inflammation are suspected to play a key role in the development of autoimmune diseases. Acquired myasthenia gravis (MG) is an invalidating neuromuscular disease leading to muscle weaknesses. MG is mainly mediated by anti-acetylcholine receptor (AChR) autoantibodies, and thymic hyperplasia characterized by ectopic germinal centers is a common feature in MG. An abnormal expression of certain TLRs is observed in the thymus of MG patients associated with the overexpression of interferon (IFN)-β, the orchestrator of thymic changes in MG...
February 2017: Clinical Reviews in Allergy & Immunology
Shan Wang, Heng Li, Min Zhang, Long-Tao Yue, Cong-Cong Wang, Peng Zhang, Ying Liu, Rui-Sheng Duan
Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells)...
July 28, 2016: Neuroscience Letters
Heng Li, Min Zhang, Cong-Cong Wang, Xiao-Li Li, Peng Zhang, Long-Tao Yue, Shuai Miao, Ying-Chun Dou, Yan-Bin Li, Rui-Sheng Duan
The Rho/Rho kinase (ROCK) pathway serves as molecular switches in many biological processes including the immune response. ROCK inhibitors lead to amelioration of some autoimmune diseases. The present study was designed to define whether a selective ROCK inhibitor, fasudil, was effective in experimental autoimmune myasthenia gravis (EAMG) and investigate the underlying mechanisms. Here we found fasudil effectively attenuated the development of ongoing EAMG. Fasudil abolished the antibody production and function by decreasing follicular helper T cells and CD19(+) B cells, especially germinal center B cells...
July 2016: Molecular and Cellular Neurosciences
Renato Mantegazza, Chiara Cordiglieri, Alessandra Consonni, Fulvio Baggi
Myasthenia gravis (MG) is a chronic autoimmune disease caused by the immune attack of the neuromuscular junction. Antibodies directed against the acetylcholine receptor (AChR) induce receptor degradation, complement cascade activation, and postsynaptic membrane destruction, resulting in functional reduction in AChR availability. Besides anti-AChR antibodies, other autoantibodies are known to play pathogenic roles in MG. The experimental autoimmune MG (EAMG) models have been of great help over the years in understanding the pathophysiological role of specific autoantibodies and T helper lymphocytes and in suggesting new therapies for prevention and modulation of the ongoing disease...
2016: International Journal of General Medicine
Canan Ulusoy, Noushin Zibandeh, Selin Yıldırım, Nikolaos Trakas, Paraskevi Zisimopoulou, Melike Küçükerden, Hatice Tașlı, Socrates Tzartos, Kamil Göker, Erdem Tüzün, Tunç Akkoç
BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5-10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared...
2015: Journal of Neuroinflammation
Jian Rong Sheng, Songhua Quan, Betty Soliven
IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. In our previous study, adoptive transfer of CD1d(hi)CD5(+) B cells expanded in vivo by GM-CSF prevented and suppressed experimental autoimmune myasthenia gravis (EAMG). The goal of this study was to further examine the role and mechanism of IL-10 in the regulatory function of B10 cells in EAMG. We found that only IL-10 competent CD1d(hi)CD5(+) B cells sorted from WT mice, but not IL-10 deficient CD1d(hi)CD5(+) B cells exhibited regulatory function in vitro and in vivo...
December 15, 2015: Journal of Neuroimmunology
Kazunobu Takahashi, Tomohisa Niiya, Yukimasa Takada, Eichi Narimatsu, Michiaki Yamakage
BACKGROUND: Train-of-four ratio (TOFR) is often used to evaluate muscle relaxation caused by neuromuscular-blocking agents (NMBAs). However, it is unknown whether TOFR reliably correlates with the first twitch tension (T1) in patients with myasthenia gravis (MG). By using rat models of experimental autoimmune MG (EAMG), the authors verified the hypothesis that the severity of MG influences the relationship between TOFR and T1. METHODS: EAMG rats were divided into sham, moderate MG, and severe MG groups...
February 2016: Anesthesiology
Xiaorong Wu, Erdem Tuzun, Shamsher S Saini, Jun Wang, Jing Li, Leopoldo Aguilera-Aguirre, Ruksana Huda, Premkumar Christadoss
Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR)...
December 2015: Immunology Letters
Revital Aricha, Debby Reuveni, Sara Fuchs, Miriam C Souroujon
Adoptive transfer of regulatory T (Treg) cells have been employed effectively for suppression of several animal models for autoimmune diseases. In order to employ Treg cell therapy in patients, it is necessary to generate Treg cells from the patient's own cells (autologous) that would be able to suppress effectively the disease in vivo, upon their reintroduction to the patient. Towards this objective, we report in the present study on a protocol for a successful immune-regulation of experimental autoimmune myasthenia gravis (EAMG) by ex vivo--generated autologous Treg cells...
February 2016: Journal of Autoimmunity
Yao-Xian Yue, Yu Hong, Yanchen Xie, Hong-Jun Hao, Yi Sui, Chuan-Kai Gu, Xu Zhang, Xiang Gao, Tian-Ping Tang, Xian-Jun Zhang, Qi Wang, Hai-Feng Li
Alleles of IL-17A and IL-17F genes were reported to be associated with many inflammatory and autoimmune disorders in Asian patients. Serum level and mRNA of IL-17A in peripheral blood mononuclear cells were reported to be significantly higher in MG patients than in healthy controls. In experimental autoimmune myasthenia gravis (EAMG) animals, IL-17 may have effects on the severity of MG. This study investigated the association between four SNPs of IL-17A and IL-17F gene (rs8193036, rs2275913 and rs3748067 in IL-17A; rs763780 in IL-17F) and MG in Chinese patients...
January 2016: Neurological Sciences
Heng Li, Cong-Cong Wang, Min Zhang, Xiao-Li Li, Peng Zhang, Long-Tao Yue, Shuai Miao, Shan Wang, Ying Liu, Yan-Bin Li, Rui-Sheng Duan
We previously demonstrated that atorvastatin induced immature dendritic cells (DCs) derived from spleen in vitro. Administration of these tolerogenic DCs led to amelioration of experimental autoimmune myasthenia gravis (EAMG). The protective effect was mainly mediated by inhibited cellular immune response, including up-regulated regulatory T cells and shifted Th1/Th17 to Th2 cytokines. The present study employed atorvastatin-modified bone marrow-derived DCs (AT-BMDCs) to explore the effect of tolerogenic DCs on humoral immune response of EAMG and further elucidate the underlying mechanisms...
September 2015: Molecular and Cellular Neurosciences
Jie Luo, Jon Lindstrom
Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR)...
October 15, 2015: Biochemical Pharmacology
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