scholarly journals Decreased expression of circulating Aire and increased Tfh/Tfr cells in myasthenia gravis patients

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Sijia Zhao ◽  
Jiaqi Ding ◽  
Shengyuan Wang ◽  
Chuan Li ◽  
Peng Guo ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Human Peripheral Blood ◽  
Autoimmune Disorder ◽  
Postsynaptic Membrane ◽  
Control Group ◽  
Significant Relation ◽  
Thymic Tissue ◽  
Follicular Helper ◽  
Lower Expression

Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells (we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T-follicular helper (cTfh) and T-follicular regulatory (cTfr) cells in MG patients. In our research, we found that the acetylcholine receptor (AChR) Ab level is higher in generalized MG (GMG) than that in ocular MG (OMG). Compared with the control group (CG), lower expression of Aire was found in MG patients, especially in GMG. The ratio of Tfh/Tfr was higher in GMG patients, and then in the OMG patients, and lowest in CG. All these differences above were statistically significant. Negative relation was discovered between expression of Aire in circulating blood and ratio of Tfh/Tfr, so did it exist between Aire expression and the severity of MG. Meanwhile, positive relation was discovered between ratio of Tfh/Tfr and the severity of MG. However, no significant relation was manifested in our study between the subset age of MG and Aire level. Overall, these findings imply circulating Aire might play a role in the imbalance of cTfh and cTfr cells and participate in the pathogenesis of MG.

scholarly journals Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis

2019 ◽  
Vol 11 (9) ◽  
pp. 4039-4048 ◽  
Author(s):  
Feng Li ◽  
Ya Tao ◽  
Gero Bauer ◽  
Aron Elsner ◽  
Zhongmin Li ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Thymic Tissue

scholarly journals HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR

Blood ◽  
2020 ◽  
Vol 135 (26) ◽  
pp. 2413-2419 ◽  
Author(s):  
Kazuya Sakai ◽  
Masataka Kuwana ◽  
Hidenori Tanaka ◽  
Kazuyoshi Hosomichi ◽  
Atsushi Hasegawa ◽  
...  
Keyword(s):  
Protective Factors ◽  
Protective Factor ◽  
Autoimmune Disorder ◽  
Japanese Patients ◽  
Control Group ◽  
Predisposing Factor ◽  
Binding Motifs ◽  
Hla Dr ◽  
Immune Mediated

Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.

scholarly journals Thymectomy in Myasthenia Gravis

2018 ◽  
Vol 2 (02) ◽  
pp. E124-E130
Author(s):  
Jens Rückert ◽  
Marc Swierzy ◽  
Siegfried Kohler ◽  
Andreas Meisel ◽  
Mahmoud Ismail
Keyword(s):  
Minimally Invasive ◽  
Myasthenia Gravis ◽  
Median Sternotomy ◽  
Surgical Techniques ◽  
Thymic Tissue ◽  
Unilateral Approach ◽  
Immunosuppressive Medication ◽  
Receptor Antibodies ◽  
Made In

AbstractIn recent years much progress has been made in the investigation of the pathophysiology, characterizing subgroups, and extension of multimodal treatment of myasthenia gravis (MG). This applies especially to the role of thymectomy (Thx). Thymectomy is always indicated for thymoma-associated myasthenia gravis. Furthermore, based on large cohort studies, during recent decades thymectomy has also become a central part of immune-modulating MG therapy in patients without thymoma. The lack of randomized studies, however, caused a certain persistent reluctance as to the significance of thymectomy. The current MGTX trial has shown the effectiveness of thymectomy. A significant improvement of myasthenic complaints and the reduction of immunosuppressive medication was primarily shown for acquired early-onset MG (EOMG) with complete resection of all thymic tissue. Because the MGTX study only included patients younger than 65 years with generalized MG and positive for acetylcholine-receptor antibodies, at present the significance of Thx for other relevant subgroups as juvenile MG, MG in older patients, ocular MG, as well as seronegative patients is under investigation. Even the prevailing opinion of no benefit of thymectomy for MuSk-positive patients probably needs reevaluation based on ambiguous findings. With respect to surgery, based on the exclusive performance of extended median sternotomy for MG in the MGTX, the value of thoracoscopic modifications for thymectomy as a minimally-invasive alternative is currently under evaluation. For clinical reasons further judgment regarding different minimally-invasive thymectomy techniques compared to the conventional open procedures in the form of randomized comparative studies would be required. Currently, however, an experience-based robotic-assisted thoracoscopic unilateral approach to thymectomy meets all requirements related to surgical, clinical-neurological and patient aspects. Ethical reasons, therefore, will lead to other strategies for comparison of different surgical techniques.

scholarly journals Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis : A prospective study

2021 ◽  
Vol 74 (1-2) ◽  
pp. 33-40
Author(s):  
Mecbure Nalbantoglu ◽  
Mehmet Ali Akalin ◽  
Aysegul Gunduz ◽  
Meral Kiziltan
Keyword(s):  
Myasthenia Gravis ◽  
Autonomic Dysfunction ◽  
Acetylcholinesterase Inhibitors ◽  
Sympathetic Skin Response ◽  
Autoimmune Disorder ◽  
Control Group ◽  
Negative Group ◽  
Achr Antibody ◽  
Skin Response ◽  
A Prospective Study

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Rituximab in AChR subtype of myasthenia gravis: systematic review

2020 ◽  
Vol 91 (4) ◽  
pp. 392-395 ◽  
Author(s):  
Vincenzo Di Stefano ◽  
Antonino Lupica ◽  
Marianna Gabriella Rispoli ◽  
Antonio Di Muzio ◽  
Filippo Brighina ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Autoimmune Disorder ◽  
Postsynaptic Membrane ◽  
Receptor Subtype ◽  
Registration Number ◽  
Randomised Controlled ◽  
Time To Relapse

Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype. The authors undertook a literature search during the period of 1999–2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients’ evaluation, ranging from a minimum of two to a maximum of three cycles. RTX led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. Treatment with RTX appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed. Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment. Trial registration number: NCT02110706.

scholarly journals Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Steven P. Luckman ◽  
Nils Erik Gilhus ◽  
Fredrik Romi
Keyword(s):  
Myasthenia Gravis ◽  
Neurological Disorders ◽  
Critical Role ◽  
Control Group ◽  
Healthy Controls ◽  
Stroke Patients ◽  
Pathogenic Role ◽  
Matrix Metalloproteinase 3 ◽  
Very High

MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signaling by controlling acetylcholine receptor clustering. High MMP-3 levels in a proportion of myasthenia gravis (MG) patients have been reported. A pathogenic role of MMP-3 in other neurological disorders has been suggested but not proven. We have therefore examined the levels of MMP-3 in 124 MG patients and compared them to 59 multiple sclerosis (MS) patients, 74 epilepsy patients, 33 acute stroke patients, and 90 healthy controls. 15.3% of the patients in the MG group were MMP-3-positive (defined as higher than cutoff value 48 ng/mL) with very high mean MMP-3 concentration (79.9 ng/mL), whereas the proportion of MMP-3 positive patients in the MS (3.4%), epilepsy (6.7%), stroke (0%), and the control group (4.4%) was significantly lower. Mean MMP-3 concentration in the total MG group (25.5 ng/mL) was significantly higher than in the MS (16.6 ng/mL) and stroke (11.7 ng/mL) groups, but did not differ significantly from the epilepsy (19.4 ng/mL) and the control group (23.4 ng/mL). MMP-3 may have a specific pathogenic effect in MG in addition to being associated with autoimmune diseases in general.

scholarly journals Transcriptome Sequencing Reveals Gene Expression Differences in the Response of Malignant Melanomas Cells to Hypoxia

2021 ◽  
Author(s):  
Haiting Xu ◽  
Huazhen Liu ◽  
Zi Li ◽  
Qin Xu ◽  
Nan Lin ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Luciferase Assay ◽  
Control Group ◽  
Rna Seq ◽  
Positive Effects ◽  
Cell Hypoxia ◽  
Group A ◽  
Hypoxic Group ◽  
Lower Expression

Abstract BackgroundMalignant melanoma (MM) is the most deadly type of skin cancer, with 5-year survival rate of less than 16%. HIF-1α overexpression is associated with poor prognosis in many cancers including MM. Hence, we characterized differentially expressed genes (DEGs) in the response of MM cells to normal and hypoxia. MethodsWe first successfully constructed cell hypoxia model and then performed RNA-seq to explore the changes of gene transcription in MM cells during hypoxia. The highest expression of the six genes was detected using qRT-PCR and western blot assays. We explored the binding sites between BIRC7 promoter and HIF-1α by dual-luciferase assay. Cellular function assays were used to observe the role of BIRC7 in the effect of hypoxia on tumor progression. ResultsWe found that compared with the transcriptome data of the control group, a total of 2601 DEGs were identified in the hypoxic group. There were 1517 genes with significantly higher expression and 1084 genes with lower expression in the hypoxic group. Among them, OSCAR, BIRC7, HBA1, SFN, GOLT1A, and BEX2 were significantly up-regulated in the hypoxic group. BIRC7 expression was most significantly up-regulated and a downstream factor of HIF-1α. We highlighted that knockdown of BIRC7 reversed the positive effects of HIF-1α on A875 and M14 cells. ConclusionsOur findings demonstrated that BIRC7 was a downstream factor of HIF-1α and reversed the effect of hypoxia on promoting tumor progression of MM cells.

scholarly journals THE ROLE OF ACALYPHA INDICA LINN. EXTRACT ON HEART RATES WITH MYASTHENIA GRAVIS RAT MODEL

2018 ◽  
Vol 11 (1) ◽  
pp. 257
Author(s):  
Desak Gede Budi Krisnamurti ◽  
Rani Wardani Hakim ◽  
Radiana Dhewayani Antarianto ◽  
Siti Farida ◽  
Erni Hernawati Purwaningsih ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Sympathetic Activity ◽  
Postsynaptic Membrane ◽  
Causal Connection ◽  
Short Term ◽  
Immune Attack ◽  
Therapeutic Development ◽  
Acalypha Indica ◽  
Experimental Autoimmune

  Objective: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. Acetylcholine is also used as a neurotransmitter in the autonomic nervous system. Striated cardiac muscle can be a target for immune attack manifesting as heart failure, arrhythmia, and sudden death. Involvement of the heart rate (HR) has been claimed and reported, but a causal connection between MG and altered cardiac function has not been found.Methods: For this study of experimental autoimmune MG (EAMG) is used rocuronium, prostigmine, and Acalypha indica (AI) Linn. compared with HR.Results: From the results, the study found that sympathetic activity of HR variability in EAMG injected with rocuronium 10 mg/kg body weight (BW) in 10 min significantly found increasing in measures of short-term variations in HR variability, indicating parasympathetic impairment.Conclusion: We conclude that in MG, cholinergic transmission is affected more diffusely than previously thought. Furthermore, AI was given orally 30 mg/kg BW has an effect similar to the injecting of prostigmine 10 mg/kg BW that can reduce HR. Driven by the fact that the pharmacological treatment of MG is unsatisfied, it needs the therapeutic development for MG using herbal ingredients of AI. This means that the AI compositions containing anti-MG whose composition should be investigated for the next research.

Myasthenia Gravis

2013 ◽  
Author(s):  
Aaron E. Miller ◽  
Teresa M. DeAngelis
Keyword(s):  
Surgical Treatment ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Diagnostic Testing ◽  
Autoimmune Disorder ◽  
Postsynaptic Membrane ◽  
Treatment Recommendations ◽  
Clinical Findings

Myasthenia gravis (MG) is an autoimmune disorder that results in loss of functional acetylcholine receptors (AChR) on the postsynaptic membrane of the neuromuscular junction caused by the presence of antibodies to the AChR. In this chapter, we review the cardinal clinical findings of MG, the standard diagnostic testing including electrophysiological features, and the medical and surgical treatment recommendations.

scholarly journals Role of Interleukin-28B in clearance of HCV in acute and chronic hepatitis patients in Kirkuk city

2018 ◽  
pp. 146-149
Author(s):  
Muhannad Abdullah Alazzawy
Keyword(s):  
Blood Donation ◽  
Cross Sectional Study ◽  
Control Group ◽  
Significant Relation ◽  
Cross Sectional ◽  
Hepatitis Patient ◽  
Acute Hcv ◽  
Chronic Hcv ◽  
Acute And Chronic Hepatitis

A cross sectional study was conducted in Kirkuk city from June 2017 to March 2018. The number of hepatitis patient understudy were 62 hepatitis C (27 acute and 35 chronic) whose ages were between 20-75 years old. The purpose of this study was to evaluate the effect of IL28B in the clearance of HCV. These patients admitted to Hepatology and Gastroenterology centers of Kirkuk. The control group who were matched to the patients studied, included 30 individuals who admitted to blood bank for blood donation, for molecular test of HCV Real-time quantitative test and serum IL-28B ELISA. The study exhibited that 81.48 % of acute HCV patient who positive by ELISA were positive by PCR and 82.86 % of chronic HCV patients were positive by PCR with highly significant relation between them. Regarding the relation of IL-28B with HCV infection, the study presented that the highest mean of IL-28B was recorded among PCR –ve acute HCV patients (17.78 pg/ml) followed by PCR +ve acute HCV and the lowest means was found in the control group with highly significant differences among the groups.  The study indicated that the highest mean of IL-28B was recorded among PCR –ve chronic HCV patients (17.78 pg/ml) followed by PCR +ve chronic HCV and the lowest means was found in the control group with highly significant relation.  The study showed that the highest mean of ALT and AST were found in acute HCV patients (72.06 and 36.73 IU/ml) respectively followed by chronic HCV and the control group with highly significant relation among the groups.

Sign in / Sign up

Export Citation Format

Share Document