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Autoimmune myasthenia

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https://www.readbyqxmd.com/read/29138598/familial-aggregation-of-myasthenia-gravis-in-affected-families-a-population-based-study
#1
Fu-Chao Liu, Chang-Fu Kuo, Lai-Chu See, Hsin-I Tsai, Huang-Ping Yu
Introduction: Myasthenia gravis (MG) is clinically heterogeneous and can be life-threatening if bulbar or respiratory muscles are involved. However, relative contributions of genetic, shared, and nonshared environmental factors to MG susceptibility remain unclear. The aim of this study was to examine the familial aggregation and heritability of MG and the relative risks (RRs) of other autoimmune diseases in the relatives of patients with MG. Methods: A population-based family study using the Taiwan National Health Insurance (NHI) Database was conducted...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29125185/thymus-involvement-in-early-onset-myasthenia-gravis
#2
REVIEW
Mélanie A Cron, Solène Maillard, José Villegas, Frédérique Truffault, Muriel Sudres, Nadine Dragin, Sonia Berrih-Aknin, Rozen Le Panse
It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125182/circulating-micrornas-as-potential-biomarkers-in-myasthenia-gravis-patients
#3
REVIEW
Anna Rostedt Punga, Tanel Punga
MicroRNAs (miRNAs) are small noncoding RNA molecules that bind to specific mRNA targets and regulate a wide range of important biological processes within cells. Circulating miRNAs are released into the extracellular space and can be measured in most biofluids, including blood serum and plasma. Recently, circulating miRNAs have emerged as easily accessible markers in various body fluids with different profiles and quantities specific for different human disorders, including autoimmune diseases. In myasthenia gravis (MG), diagnostic tests such as titers of serum autoantibodies specific for either the acetylcholine receptor (AChR(+) ) or muscle-specific tyrosine kinase (MuSK(+) ) do not necessarily reflect disease progression, and there is a great need for reliable objective biomarkers to monitor the disease course and therapeutic response...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29121404/the-association-of-british-neurologists-myasthenia-gravis-guidelines
#4
Jon Sussman, Maria E Farrugia, Paul Maddison, Marguerite Hill, M Isabel Leite, David Hilton-Jones
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era of evidence-based medicine. Despite the basic principles of treatment being well known, patients continue to receive suboptimal treatment. A myasthenia gravis guidelines group was therefore established under the aegis of the Association of British Neurologists. These guidelines attempt to steer a path between evidence-based practice where available and established best practice where evidence is unavailable...
November 9, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29114250/a-sensitive-method-for-detecting-peptide-specific-cd4-t-cell-responses-in-peripheral-blood-from-patients-with-myasthenia-gravis
#5
Sapna Sharma, Clas Malmeström, Christopher Lindberg, Sarah Meisel, Karin Schön, Martina Verolin, Nils Yngve Lycke
Myasthenia gravis (MG) is an autoimmune neurological disorder typified by skeletal muscle fatigue and most often production of autoantibodies against the nicotinic acetylcholine receptor (AChR). The present study was undertaken to assess the extent of AChR-peptide recognition in MG patients using co-culturing (DC:TC) of autologous monocyte-derived dendritic cells (moDCs) and highly enriched CD4(+) T cells from the blood as compared to the traditional whole peripheral blood mononuclear cell (PBMC) cultures. We found that the DC:TC cultures were highly superior to the PBMC cultures for detection of reactivity toward HLA-DQ/DR-restricted AChR-peptides...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29104781/the-minor-variant-of-the-single-nucleotide-polymorphism-rs3753381-affects-the-activity-of-a-slamf1-enhancer
#6
L V Putlyaeva, A M Schwartz, A V Klepikova, I E Vorontsov, I V Kulakovskiy, D V Kuprash
The SLAMF1 gene encodes CD150, a transmembrane glycoprotein expressed on the surface of T and B-lymphocytes, NK-cells, dendritic cells, and subpopulations of macrophages and basophils. We investigated the functional regulatory polymorphisms of the SLAMF1 locus associated with autoimmune processes, using bioinformatics and a mutational analysis of the regulatory elements overlapping with polymorphic positions. In the reporter gene assay in MP-1 and Raji B-cell lines, the enhancer activity of the regulatory region of the locus containing the rs3753381 polymorphism demonstrated a twofold increase upon the introduction of the rs3753381 minor variant (G → A) associated with myasthenia gravis...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/29083502/a-clinical-predictive-score-for-postoperative-myasthenic-crisis
#7
Tetsuya Kanai, Akiyuki Uzawa, Yasunori Sato, Shigeaki Suzuki, Naoki Kawaguchi, Keiichi Himuro, Fumiko Oda, Yukiko Ozawa, Jin Nakahara, Norihiro Suzuki, Yuko K Takahashi, Satoru Ishibashi, Takanori Yokota, Takashi Ogawa, Kazumasa Yokoyama, Nobutaka Hattori, Shoko Izaki, Satoru Oji, Kyoichi Nomura, Juntaro Kaneko, Kazutoshi Nishiyama, Ichiro Yoshino, Satoshi Kuwabara
OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis...
October 30, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29078673/the-results-of-video-assisted-thoracoscopic-thymectomies-in-saint-petersburg-russia-20-year-of-experience
#8
Piotr Yablonsky, Vadim Pischik, Marina G Tovbina, Mikhail Atiukov
BACKGROUND: During the period from 1996 to 2016, we have performed 281 thymectomies in patients with various diseases of the thymus. In 179 patients, thymic pathology was associated with autoimmune myasthenia gravis (MG), and, in 108 patients, thymoma was diagnosed. METHODS: The majority of surgeries [254] were performed using video thoracoscopy, 79 of them with an additional cervical approach. The long-term results of video thoracoscopic thymectomies in myasthenic patients were followed up for 1 to 15...
2017: J Vis Surg
https://www.readbyqxmd.com/read/29073308/15-year-old-girl-with-aps-type-iiic-12-months-post-thymectomy-remission-of-myasthenia
#9
Milena Jamiołkowska, Artur Bossowski
Polyglandular autoimmune syndromes (PAS) is a group of heterogenous conditions characterized by the association of at least two organ-specific autoimmune disorders, concerning both endocrine and non-endocrine organs. Type III is defined as the combination of autoimmune thyroid disease and other autoimmune condition (other than Addison's disease) and is divided into four subtypes. We describe a teenage female patient - with the family history of autoimmune diseases, who has simultaneously developed the symptoms of autoimmune thyroid disease with the clinical picture of hyperthyroidism and myasthenia gravis at the age of fifteen...
2017: Pediatric Endocrinology, Diabetes, and Metabolism
https://www.readbyqxmd.com/read/29068555/diagnostic-utility-of-cortactin-antibodies-in-myasthenia-gravis
#10
REVIEW
Isabel Illa, Elena Cortés-Vicente, María Ángeles Martínez, Eduard Gallardo
Patients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as having double-seronegative myasthenia gravis (dSNMG). We used the sera from six dSNMG patients with positive immunohistochemistry assays in a protein array to screen reactivity with 9000 human proteins. We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen in dSNMG. We then designed an in-house enzyme-linked immunosorbent assay as a screening assay and confirmed these results by western blot...
October 25, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29057629/the-impacts-of-influenza-infection-and-vaccination-on-exacerbation-of-myasthenia-gravis
#11
Hung Youl Seok, Ha Young Shin, Jong Kuk Kim, Byoung Joon Kim, Jeeyoung Oh, Bum Chun Suh, Sun Young Kim, Sa Yoon Kang, Suk Won Ahn, Jong Seok Bae, Byung Jo Kim
BACKGROUND AND PURPOSE: Upper respiratory infection (URI), including influenza, may exacerbate the symptoms of myasthenia gravis (MG), which is an autoimmune disease that causes muscle weakness. There is also concern that the influenza vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of influenza infection and vaccination on symptom severity in MG patients. METHODS: Patients diagnosed with MG were enrolled from 10 university-affiliated hospitals between March and August 2015...
October 2017: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/29040265/analysis-of-peripheral-b-cells-and-autoantibodies-against-the-anti-nicotinic-acetylcholine-receptor-derived-from-patients-with-myasthenia-gravis-using-single-cell-manipulation-tools
#12
Tomohiro Makino, Ryuichi Nakamura, Maki Terakawa, Satoshi Muneoka, Kazuhiro Nagahira, Yuriko Nagane, Jyoji Yamate, Masakatsu Motomura, Kimiaki Utsugisawa
The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization...
2017: PloS One
https://www.readbyqxmd.com/read/29036181/juvenile-myasthenia-gravis-in-norway-hla-drb1-04-04-is-positively-associated-with-prepubertal-onset
#13
T H Popperud, M K Viken, E Kerty, B A Lie
BACKGROUND: Juvenile myasthenia gravis (MG) is a rare autoantibody mediated autoimmune disorder targeting the neuromuscular endplate. The clinical hallmark is muscle weakness and fatigability. Disease aetiology is complex, including both genetic and environmental factors. The involvement of genes in the human leukocyte antigen (HLA) is well established in adult MG. However, HLA associations in European juvenile MG have not been studied. This case-control study aimed to investigate and characterize genetic risk factors in prepubertal and postpubertal onset juvenile MG...
2017: PloS One
https://www.readbyqxmd.com/read/29034433/development-of-humanized-scfv-antibody-fragment-s-that-targets-and-blocks-specific-hla-alleles-linked-to-myasthenia-gravis
#14
B Vijayalakshmi Ayyar, M Zouhair Atassi
Myasthenia gravis (MG) is an autoimmune disease caused by sensitization of the immune system to self-antigens. We have previously shown that targeting MG-susceptible alleles can significantly inhibit proliferation of disease-specific T cells. In this work, we humanized a murine monoclonal antibody (mAb) LG11, capable of blocking MG-associated DQ beta 1 (DQB1) allele and reformatted it into single-chain fragment variable (scFv). A fully functional humanized scFv was obtained by optimizing variable domain orientations and linker lengths, along with the optimization of expression conditions and codons to suit Escherichia coli expression machinery...
October 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28972088/nfat1-regulates-systemic-autoimmunity-through-the-modulation-of-a-dendritic-cell-property
#15
Chang-Suk Chae, Gi-Cheon Kim, Eun Sil Park, Choong-Gu Lee, Ravi Verma, Hagg-Lim Cho, Chang-Duk Jun, Yung Joon Yoo, Sin-Hyeog Im
The transcription factor NFAT1 plays a pivotal role in the homeostasis of T lymphocytes. However, its functional importance in non-CD4(+) T cells, especially in systemic immune disorders, is largely unknown. In this study, we report that NFAT1 regulates dendritic cell (DC) tolerance and suppresses systemic autoimmunity using the experimental autoimmune myasthenia gravis (EAMG) as a model. Myasthenia gravis and EAMG are T cell-dependent, Ab-mediated autoimmune disorders in which the acetylcholine receptor is the major autoantigen...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28970832/use-of-toll-like-receptor-agonists-to-induce-ectopic-lymphoid-structures-in-myasthenia-gravis-mouse-models
#16
Marieke Robinet, Bérengère Villeret, Solène Maillard, Mélanie A Cron, Sonia Berrih-Aknin, Rozen Le Panse
Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. MG symptoms are characterized by muscle weaknesses. The thymus of MG patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development. We previously demonstrated that injections of mice with polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic double-stranded RNA mimicking viral infection, induce thymic changes and trigger MG symptoms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28959261/a-novel-approach-to-reinstating-tolerance-in-experimental-autoimmune-myasthenia-gravis-using-a-targeted-fusion-protein-mcta1-t146
#17
Alessandra Consonni, Sapna Sharma, Karin Schön, Cristina Lebrero-Fernández, Elena Rinaldi, Nils Yngve Lycke, Fulvio Baggi
Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR) at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28954337/-clinical-analysis-of-paraneoplastic-neurological-syndrome-associated-with-thymoma
#18
H S Liu, H T Ren, L X Zhou, S Q Li, B Peng, L Y Cui, H Z Guan
Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected...
September 19, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28941526/pediatric-myasthenia-gravis
#19
Jason H Peragallo
Myasthenia gravis is a disorder of neuromuscular transmission that leads to fatigue of skeletal muscles and fluctuating weakness. Myasthenia that affects children can be classified into the following 3 forms: transient neonatal myasthenia, congenital myasthenic syndromes, and juvenile myasthenia gravis (JMG). JMG is an autoimmune disorder that has a tendency to affect the extraocular muscles, but can also affect all skeletal muscles leading to generalized weakness and fatigability. Respiratory muscles may be involved leading to respiratory failure requiring ventilator support...
May 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28940642/b-cells-in-the-pathophysiology-of-myasthenia-gravis
#20
REVIEW
John S Yi, Jeffrey T Guptill, Panos Stathopoulos, Richard J Nowak, Kevin C O'Connor
Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients, or to muscle-specific tyrosine kinase (MuSK) in others, and to a growing number of other postsynaptic proteins in smaller subsets. A decrease in the number of functional acetylcholine receptors (AChR), or functional interruption of the AChR, within the muscle end plate of the neuromuscular junction is caused by pathogenic autoantibodies. Although the molecular immunology underpinning the pathology is well understood, much remains to be learned about the cellular immunology contributing to the production of autoantibodies...
September 20, 2017: Muscle & Nerve
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