Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction.＂Warming yang and inv...Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction.＂Warming yang and invigorating qi＂ acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis.However,few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction.Here,we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following ＂warming yang and invigorating qi＂ acupuncture therapy.Needles were inserted at acupressure points Shousanli（LI10）,Zusanli（ST36）,Pishu（BL20）,and Shenshu（BL23） once daily for 7 consecutive days.The treatment was repeated after 1 day of rest.We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment.This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide.These findings suggest that ＂warming yang and invigorating qi＂ acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.展开更多
Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix （PCRR） and its ingredient resveratrol （Res） on experimental autoimmune myasthenia gravis （EAMG）. Methods EAMG was induced in Lewis rats...Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix （PCRR） and its ingredient resveratrol （Res） on experimental autoimmune myasthenia gravis （EAMG）. Methods EAMG was induced in Lewis rats by the immunization of a synthetic peptide corresponding to region 97-116 of the rat acetylcholine receptor （AChR） α subunit （R97-116）. EAMG rats were randomly divided into PCRR group, Res group, and control （C） group, and were ig administered respectively with PCRR （2 g/kg）, Res （20 mg/kg）, and DMSO （0.4 mL/kg） every day from day 5 after immunization to day 42. Clinical evaluation, lymphocyte proliferation, cytokines, and anti-97-116 antibodies were performed for examination of their therapeutic effects. Results Treatments with PCRR and Res significantly ameliorated clinical symptoms, down-regulated TNF-α and up-regulated IL-10 in serum and culture supernatants of lymphocytes stimulated with R97-116, and decreased levels of anti-R97-116 IgG1 and IgG2a in serum compared with C group. Unexpectedly, PCRR but not Res inhibited lymphocyte proliferation compared with C group. Conclusion PCRR and Res ameliorating EAMG is associated with suppressing immune response, and indicates a therapeutic potential for EAMG and even human myasthenia gravis （MG）. Res may be the main effective ingredient from PCRR ameliorating EAMG, but further experiments are necessary.展开更多
Myasthenia gravis(MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper(Tfh) cells have been implicated in ma...Myasthenia gravis(MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper(Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear.Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha(AChRa) subunit(RAChR97–116)-induced experimental autoimmune myasthenia gravis(EAMG). This model presented mild bodyweight loss 10 days after the first immunization(representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization(representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In cocultures of Tfh cells and B cells, the number of IgG2 bsecreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4^+/Bcl-6^+ T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, wehypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.展开更多
Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the m...Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.展开更多
Anti-acetylcholine receptor antibodies （AAR） are considered pathognomonic and pathogenetic for myasthenia gravis （MG）. AAR detection confirms clinical diagnosis of MG. However, AAR is rarely detected in patients w...Anti-acetylcholine receptor antibodies （AAR） are considered pathognomonic and pathogenetic for myasthenia gravis （MG）. AAR detection confirms clinical diagnosis of MG. However, AAR is rarely detected in patients without MG. The underlying pathophysiological mechanisms in a normal subject without MG have not been adequately addressed in previous studies. The present study reports on a case study of a healthy, elderly man with high AAR titers for 14 years. Pathophysiological mechanisms could be due to AAR heterogeneity in specificity, affinity, and multiform, and to muscle variability in response to AAR.展开更多
Single-chain variable domain fragment （scFv） 637 is an antigen-specific scFv of myasthenia gravis. In this study, scFv and human serum albumin genes were conjugated and the fusion pro-tein was expressed in Pichia pa...Single-chain variable domain fragment （scFv） 637 is an antigen-specific scFv of myasthenia gravis. In this study, scFv and human serum albumin genes were conjugated and the fusion pro-tein was expressed in Pichia pastoris. The afifnity of scFv-human serum albumin fusion protein to bind to acetylcholine receptor at the neuromuscular junction of human intercostal muscles was detected by immunolfuorescence staining. The ability of the fusion protein to block myas-thenia gravis patient sera binding to acetylcholine receptors and its stability in healthy serum were measured by competitive ELISA. The results showed that the inhibition rate was 2.0-77.4%, and the stability of fusion protein in static healthy sera was about 3 days. This approach suggests the scFv-human serum albumin is a potential candidate for speciifc immunosuppressive therapy of myasthenia gravis.展开更多
Myasthenia gravis(MG)is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular,bulbar and limb skeletal muscles.There are two major clinical types of MG.Ocular MG(OMG)affects extra ocular...Myasthenia gravis(MG)is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular,bulbar and limb skeletal muscles.There are two major clinical types of MG.Ocular MG(OMG)affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body.Patients with OMG have painless fluctuating extra ocular muscles weakness,diplopia and ptosis accompanied by normal visual acuity and pupillary function.Frequently,patients with OMG develop generalized MG over 24 months.Pure OMG is more often earlier in onset(<45 years)than generalized MG.It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors.Diagnosis is based on clinical manifestations,laboratory findings,electrophysiological evaluation and pharmacologic tests.Therapeutic strategies for MG consist of symptom relieving medications(e.g.,acetylcholine esterase inhibitors),immunosuppressive agents,and surgical intervention(e.g.,thymectomy).展开更多
Dysphagia is a common symptom in otolaryngology, but neuromuscular causes are rarely diagnostic hypotheses to be considered. The Myasthenia Gravis is an autoimmune disease which is characterized by muscle weakness tha...Dysphagia is a common symptom in otolaryngology, but neuromuscular causes are rarely diagnostic hypotheses to be considered. The Myasthenia Gravis is an autoimmune disease which is characterized by muscle weakness that can affect the muscles of the face, oral cavity, pharynx or esophagus and may present with swallowing disorders. The authors present the case of a 68-year-old man who went to the emergency department of otolaryngology complaining of dysphagia. After the examination and diagnostic exams, it was diagnosed as Myasthenia Gravis. The authors conclude that the clinical suspicion should not be forgotten in order to initiate timely treatment to the effective control of the disease and complement with functional tests according to the complaints, so that it can be followed up and start rehabilitation of the patient.展开更多
Objective To report the presentation,clinical course and prognosis of myasthenia gravis(MG)with thyroid disease.Methods Retrospective data analysis was conducted.Between 2004 and 2013,we reviewed a total of 106 patien...Objective To report the presentation,clinical course and prognosis of myasthenia gravis(MG)with thyroid disease.Methods Retrospective data analysis was conducted.Between 2004 and 2013,we reviewed a total of 106 patients with MG.We analyzed the clinical features,the relationship between the thyroid function,an-展开更多
基金supported by the National Natural Science Foundation of China,No.81173344
文摘Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction.＂Warming yang and invigorating qi＂ acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis.However,few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction.Here,we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following ＂warming yang and invigorating qi＂ acupuncture therapy.Needles were inserted at acupressure points Shousanli（LI10）,Zusanli（ST36）,Pishu（BL20）,and Shenshu（BL23） once daily for 7 consecutive days.The treatment was repeated after 1 day of rest.We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment.This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide.These findings suggest that ＂warming yang and invigorating qi＂ acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.
文摘Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix （PCRR） and its ingredient resveratrol （Res） on experimental autoimmune myasthenia gravis （EAMG）. Methods EAMG was induced in Lewis rats by the immunization of a synthetic peptide corresponding to region 97-116 of the rat acetylcholine receptor （AChR） α subunit （R97-116）. EAMG rats were randomly divided into PCRR group, Res group, and control （C） group, and were ig administered respectively with PCRR （2 g/kg）, Res （20 mg/kg）, and DMSO （0.4 mL/kg） every day from day 5 after immunization to day 42. Clinical evaluation, lymphocyte proliferation, cytokines, and anti-97-116 antibodies were performed for examination of their therapeutic effects. Results Treatments with PCRR and Res significantly ameliorated clinical symptoms, down-regulated TNF-α and up-regulated IL-10 in serum and culture supernatants of lymphocytes stimulated with R97-116, and decreased levels of anti-R97-116 IgG1 and IgG2a in serum compared with C group. Unexpectedly, PCRR but not Res inhibited lymphocyte proliferation compared with C group. Conclusion PCRR and Res ameliorating EAMG is associated with suppressing immune response, and indicates a therapeutic potential for EAMG and even human myasthenia gravis （MG）. Res may be the main effective ingredient from PCRR ameliorating EAMG, but further experiments are necessary.
基金supported by the National Natural Science Foundation of China(81000536,81471227,31371079,31671112 and 81430035)the China Postdoctoral Science Foundation(20100471094)+3 种基金the Returned Overseas Scholars Foundation of the Natural Science Foundation of Heilongjiang Province,China(LC2015029,QC2015022)the Science and Technology Research Project of the Education Department of Heilongjiang Province,China(12541z008)the Heilongjiang Province Postdoctoral Science Foundation(LBH-Q131111)the Open Topic of Key Laboratory of Neurobiology,General Colleges and Universities in Heilongjiang Province,China(2013HLJKLNT-05)
文摘Myasthenia gravis(MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper(Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear.Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha(AChRa) subunit(RAChR97–116)-induced experimental autoimmune myasthenia gravis(EAMG). This model presented mild bodyweight loss 10 days after the first immunization(representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization(representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In cocultures of Tfh cells and B cells, the number of IgG2 bsecreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4^+/Bcl-6^+ T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, wehypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.
文摘Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.
文摘Anti-acetylcholine receptor antibodies （AAR） are considered pathognomonic and pathogenetic for myasthenia gravis （MG）. AAR detection confirms clinical diagnosis of MG. However, AAR is rarely detected in patients without MG. The underlying pathophysiological mechanisms in a normal subject without MG have not been adequately addressed in previous studies. The present study reports on a case study of a healthy, elderly man with high AAR titers for 14 years. Pathophysiological mechanisms could be due to AAR heterogeneity in specificity, affinity, and multiform, and to muscle variability in response to AAR.
基金supported by the National Natural Science Foundation of China,No.30360100,30760234,30860260,81160373,81360458
文摘Single-chain variable domain fragment （scFv） 637 is an antigen-specific scFv of myasthenia gravis. In this study, scFv and human serum albumin genes were conjugated and the fusion pro-tein was expressed in Pichia pastoris. The afifnity of scFv-human serum albumin fusion protein to bind to acetylcholine receptor at the neuromuscular junction of human intercostal muscles was detected by immunolfuorescence staining. The ability of the fusion protein to block myas-thenia gravis patient sera binding to acetylcholine receptors and its stability in healthy serum were measured by competitive ELISA. The results showed that the inhibition rate was 2.0-77.4%, and the stability of fusion protein in static healthy sera was about 3 days. This approach suggests the scFv-human serum albumin is a potential candidate for speciifc immunosuppressive therapy of myasthenia gravis.
文摘Myasthenia gravis(MG)is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular,bulbar and limb skeletal muscles.There are two major clinical types of MG.Ocular MG(OMG)affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body.Patients with OMG have painless fluctuating extra ocular muscles weakness,diplopia and ptosis accompanied by normal visual acuity and pupillary function.Frequently,patients with OMG develop generalized MG over 24 months.Pure OMG is more often earlier in onset(<45 years)than generalized MG.It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors.Diagnosis is based on clinical manifestations,laboratory findings,electrophysiological evaluation and pharmacologic tests.Therapeutic strategies for MG consist of symptom relieving medications(e.g.,acetylcholine esterase inhibitors),immunosuppressive agents,and surgical intervention(e.g.,thymectomy).
文摘Dysphagia is a common symptom in otolaryngology, but neuromuscular causes are rarely diagnostic hypotheses to be considered. The Myasthenia Gravis is an autoimmune disease which is characterized by muscle weakness that can affect the muscles of the face, oral cavity, pharynx or esophagus and may present with swallowing disorders. The authors present the case of a 68-year-old man who went to the emergency department of otolaryngology complaining of dysphagia. After the examination and diagnostic exams, it was diagnosed as Myasthenia Gravis. The authors conclude that the clinical suspicion should not be forgotten in order to initiate timely treatment to the effective control of the disease and complement with functional tests according to the complaints, so that it can be followed up and start rehabilitation of the patient.
文摘Objective To report the presentation,clinical course and prognosis of myasthenia gravis(MG)with thyroid disease.Methods Retrospective data analysis was conducted.Between 2004 and 2013,we reviewed a total of 106 patients with MG.We analyzed the clinical features,the relationship between the thyroid function,an-
