scholarly journals Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management

2020 ◽  
Vol 11 ◽  
Author(s):  
Konstantinos Lazaridis ◽  
Socrates J. Tzartos
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Disease Diagnosis ◽  
Autoimmune Response ◽  
Response To Treatment ◽  
Antibody Detection ◽  
Serological Tests ◽  
The Past

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction, characterized by skeletal muscle weakness and fatigability. It is caused by autoantibodies targeting proteins of the neuromuscular junction; ~85% of MG patients have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 5% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). In the remaining about 10% of patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG). Since serological tests are relatively easy and non-invasive for disease diagnosis, the improvement of methods for the detection of known autoantibodies or the discovery of novel autoantibody specificities to diminish SN-MG and to facilitate differential diagnosis of similar diseases, is crucial. Radioimmunoprecipitation assays (RIPA) are the staple for MG antibody detection, but over the past years, using cell-based assays (CBAs) or improved highly sensitive RIPAs, it has been possible to detect autoantibodies in previously SN-MG patients. This led to the identification of more patients with antibodies to the classical antigens AChR and MuSK and to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets, such as agrin, Kv1.4 potassium channels, collagen Q, titin, the ryanodine receptor and cortactin have been found in some MG patients. Since the autoantigen targeted determines in part the clinical manifestations, prognosis and response to treatment, serological tests are not only indispensable for initial diagnosis, but also for monitoring treatment efficacy. Importantly, knowing the autoantibody profile of MG patients could allow for more efficient personalized therapeutic approaches. Significant progress has been made over the past years toward the development of antigen-specific therapies, targeting only the specific immune cells or autoantibodies involved in the autoimmune response. In this review, we will present the progress made toward the development of novel sensitive autoantibody detection assays, the identification of new MG autoantigens, and the implications for improved antigen-specific therapeutics. These advancements increase our understanding of MG pathology and improve patient quality of life by providing faster, more accurate diagnosis and better disease management.

scholarly journals Post-Translational Modifications of Proteins: Novel Insights in the Autoimmune Response in Rheumatoid Arthritis

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 657 ◽  
Author(s):  
Francesco Carubbi ◽  
Alessia Alunno ◽  
Roberto Gerli ◽  
Roberto Giacomelli
Keyword(s):  
Rheumatoid Arthritis ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Autoimmune Response ◽  
Response To Treatment ◽  
Post Translational Modifications ◽  
Wide Range ◽  
Specific Proteins ◽  
Modified Proteins ◽  
Immunogenic Properties

Post-translational modifications (PTM) are chemical changes mostly catalyzed by enzymes that recognize specific target sequences in specific proteins. These modifications play a key role in regulating the folding of proteins, their targeting to specific subcellular compartments, their interaction with ligands or other proteins, and eventually their immunogenic properties. Citrullination is the best characterized PTM in the field of rheumatology, with antibodies anticyclic citrullinated peptides being the gold standard for the diagnosis of rheumatoid arthritis (RA). In recent years, growing evidence supports not only that a wide range of proteins are subject to citrullination and can trigger an autoimmune response in RA, but also that several other PTMs such as carbamylation and acetylation occur in patients with this disease. This induces a wide spectrum of autoantibodies, as biomarkers, with different sensitivity and specificity for diagnosis, which may be linked to peculiar clinical manifestations and/or response to treatment. The purpose of this review article is to critically summarize the available literature on antibodies against post-translationally modified proteins, in particular antibodies against citrullinated proteins (ACPA) and antibodies against modified proteins (AMPA), and outline their diagnostic and prognostic role to be implemented in clinical practice for RA patients.

scholarly journals Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1513 ◽  
Author(s):  
William D. Phillips ◽  
Angela Vincent
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Respiratory Muscles ◽  
Postsynaptic Membrane ◽  
Synaptic Function ◽  
Density Lipoprotein Receptor ◽  
Synapse Maintenance ◽  
Muscle Groups

Myasthenia gravis 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. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

scholarly journals Chagas disease: What is known and what should be improved: a systemic review

2012 ◽  
Vol 45 (3) ◽  
pp. 286-296 ◽  
Author(s):  
José Rodrigues Coura ◽  
José Borges-Pereira
Keyword(s):  
Latin America ◽  
Chagas Disease ◽  
Control Program ◽  
Response To Treatment ◽  
Systemic Review ◽  
Serological Tests ◽  
The Past ◽  
Gran Chaco ◽  
And Control ◽  
New Strategies

This study consists of a broad review on what is known and what should be improved regarding knowledge of Chagas disease, not only through analysis on the main studies published on the topics discussed, but to a large extent based on experience of this subject, acquired over the past 50 years (1961-2011). Among the subjects covered, we highlight the pathogenesis and evolution of infection by Trypanosoma cruzi, drugs in use and new strategies for treating Chagas disease; the serological tests for the diagnosis and the controls of cure the infection; the regional variations in prevalence, morbidity and response to treatment of the disease; the importance of metacyclogenesis of T. cruzi in different species of triatomines and its capacity to transmit Chagas infection; the risks of adaptation of wild triatomines to human dwellings; the morbidity and need for a surveillance and control program for Chagas disease in the Amazon region and the need to prioritize initiatives for controlling Chagas disease in Latin America and Mexico and in non-endemic countries, which is today a major international dilemma. Finally, we raise the need for to create a new initiative for controlling Chagas disease in the Gran Chaco, which involves parts of Argentina, Bolivia and Paraguay.

Immune-Mediated Disease of the Neuromuscular Junction

2019 ◽  
pp. 130-176
Author(s):  
Robert P. Lisak ◽  
James Selwa
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Rare Disease ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Diagnosis And Treatment ◽  
Future Directions ◽  
Immune Mediated ◽  
Myasthenic Syndrome

The chapter is concerned with disorders that affect the neuromuscular junction (NMJ). Myasthenia gravis (MG) is a prototypic antibody-mediated disease affecting the neuromuscular junction. The chapter looks at the epidemiology of MG. It also considers clinical manifestations and presentations, classification and staging, and diagnosis. The chapter also examines immunologic testing and issues such as pregnancy in MG. It considers future directions and treatment options in this area. Next, the chapter considers Lambert Eaton myasthenic syndrome (LEMS), which is a rare disease of the NMJ that is difficult to diagnose. The chapter looks at clinical manifestations, diagnosis, and treatment. Finally, the chapter briefly considers other immune-mediated diseases.

PCSK9 inhibition for LDL lowering and beyond – implications for patients with peripheral artery disease

VASA ◽  
2018 ◽  
Vol 47 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Katrin Gebauer ◽  
Holger Reinecke
Keyword(s):  
Cardiovascular Risk ◽  
Risk Reduction ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Past Century ◽  
Pcsk9 Inhibitors ◽  
Cardiovascular Risk Reduction ◽  
Simultaneous Application ◽  
The Past ◽  
Pcsk9 Inhibition

Abstract. Low-density lipoprotein cholesterol (LDL-C) has been proven to be a causal factor of atherosclerosis and, along with other triggers like inflammation, the most frequent reason for peripheral arterial disease. Moreover, a linear correlation between LDL-C concentration and cardiovascular outcome in high-risk patients could be established during the past century. After the development of statins, numerous randomized trials have shown the superiority for LDL-C reduction and hence the decrease in cardiovascular outcomes including mortality. Over the past decades it became evident that more intense LDL-C lowering, by either the use of highly potent statin supplements or by additional cholesterol absorption inhibitor application, accounted for an even more profound cardiovascular risk reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a serin protease with effect on the LDL receptor cycle leading to its degradation and therefore preventing continuing LDL-C clearance from the blood, is the target of a newly developed monoclonal antibody facilitating astounding LDL-C reduction far below to what has been set as target level by recent ESC/EAS guidelines in management of dyslipidaemias. Large randomized outcome trials including subjects with PAD so far have been able to prove significant and even more intense cardiovascular risk reduction via further LDL-C debasement on top of high-intensity statin medication. Another approach for LDL-C reduction is a silencing interfering RNA muting the translation of PCSK9 intracellularly. Moreover, PCSK9 concentrations are elevated in cells involved in plaque composition, so the potency of intracellular PCSK9 inhibition and therefore prevention or reversal of plaques may provide this mechanism of action on PCSK9 with additional beneficial effects on cells involved in plaque formation. Thus, simultaneous application of statins and PCSK9 inhibitors promise to reduce cardiovascular event burden by both LDL-C reduction and pleiotropic effects of both agents.

NUMERICAL COEFFICIENT FOR ENDOMETRIAL CANCER INDIVIDUAL RISK EVALUATION IN POSTMENOPAUSAL WOMEN

2017 ◽  
Vol 63 (3) ◽  
pp. 461-465
Author(s):  
Lev Bershteyn ◽  
Dmitriy Vasilev ◽  
Tatyana Poroshina ◽  
Igor Berlev
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Risk Evaluation ◽  
Tumor Response ◽  
Molecular Genetic ◽  
Response To Treatment ◽  
Individual Risk ◽  
The Past ◽  
Genetic Landscape ◽  
Numerical Coefficient

Increased frequency of endometrial cancer (EC) since the beginning of this century exceeds that of breast cancer and to a large extent can be attributed to dynamics of parameters, which characterize hormonal and metabolic status of ill women and molecular genetic landscape of transforming endometrium. During the past few years there are suggested several options for a personalized assessment of the risk of EC. The aim of this article is to propose and justify own version of this score with the idea of its further not only retrospective but also prospective testing both in relation to the risk of developing endometrial cancer as well as an additional marker helping to predict tumor response to treatment.

Etiology and clinical features of epididymo-orchitis: A single-center study in Tehran, Iran

2020 ◽  
Vol 20 ◽  
Author(s):  
Sara Abolghasemi ◽  
Mohammad Alizadeh ◽  
Ali Hashemi ◽  
Shabnam Tehrani
Keyword(s):  
Chlamydia Trachomatis ◽  
Clinical Symptoms ◽  
Urine Culture ◽  
Clinical Manifestations ◽  
Urinary Frequency ◽  
Serological Tests ◽  
Duration Of Symptoms ◽  
Two Samples ◽  
History Of ◽  
Tract Infections

Introduction: Epididymo-orchitis is a common urological disease among men. Little is known about the clinical and epidemiological aspects of the disease in Iran. Thus, the present study was aimed to investigate the etiology, clinical sequelae and risk factors of patients with epididymo-orchitis in Tehran, Iran. Materials and Methods: Patients presenting with epididymo-orchitis were prospectively analyzed in order to study the etiology and pattern of the disease. Bacteriological, molecular and serological tests were undertaken to look for Chlamydia trachomatis, Neisseria gonorrhoeae, Brucella spp., Mycoplasma spp, and other bacteria. Results: Fifty patients with epididymo-orchitis were evaluated according to their clinical symptoms, duration of symptoms, physical examination, and laboratory studies. The mean age of the patients was 53 years. Fever, dysuria, pain in the flanks, urinary frequency and discharges occurred in 58.0%, 50.0%, 50.0%, 28.0% and 6.0%, respectively. Bacterial pathogen was identified in 26% (13/50) of patients by urine culture. Escherichia coli was the etiological agent in 11/13 patients (84.6%). Two out of 50 patients (4.0%) were also positive for Chlamydia trachomatis. Two samples were serologically positive for Brucella spp. High Mean age, fever, urinary frequency, history of the underlying disease and history of urinary tract infections were found to have a significant association with the positive bacteriologic urine culture (P<0.05). Conclusions: The most common clinical manifestations were fever, dysuria, and abdominal pain. E. coli and C. trachomatis were the major causative agents. Use of a set of diagnostic approaches including clinical symptoms, urine culture and more precise techniques such as PCR should be taken into consideration for the definitive diagnosis.

Scrub typhus (Orientia tsutsugamushi), A rapidly spreading epidemic in Chennai - A standalone lab experience

2016 ◽  
Vol 5 (09) ◽  
pp. 4896
Author(s):  
Sripriya C.S.* ◽  
Shanthi B. ◽  
Arockia Doss S. ◽  
Antonie Raj I. ◽  
Mohana Priya
Keyword(s):  
Scrub Typhus ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Febrile Illness ◽  
Orientia Tsutsugamushi ◽  
The Past ◽  
Igm Elisa ◽  
The Mean ◽  
Specific Symptoms ◽  
Symptoms And Signs

Scrub typhus (Orientia tsutsugamushi), is a strict intracellular bacterium which is reported to be a recent threat to parts of southern India. There is re-emergence of scrub typhus during the past few years in Chennai. Scrub typhus is an acute febrile illness which generally causes non-specific symptoms and signs. The clinical manifestations of this disease range from sub-clinical disease to organ failure to fatal disease. This study documents our laboratory experience in diagnosis of scrub typhus in patients with fever and suspected clinical symptoms of scrub typhus infection for a period of two years from April 2014 to April 2016 using immunochromatography and IgM ELISA methods. The study was conducted on 648 patients out of whom 188 patients were found to be positive for scrub typhus. Results also showed that pediatric (0 -12 years) and young adults (20 – 39 years) were more exposed to scrub typhus infection and female patients were more infected compared to male. The study also showed that the rate of infection was higher between September to February which also suggested that the infection rate is proportional to the climatic condition. Statistical analysis showed that the mean age of the patients in this study was 37.6, standard deviation was 18.97, CV % was 50.45. 

Acute exudative paraneoplastic polymorphous vitelliform maculopathy in a patient with thymoma, myasthenia gravis, and polymyositis

2021 ◽  
pp. 112067212199404
Author(s):  
He Yu ◽  
Xinyu Ma ◽  
Nianting Tong ◽  
Zhanyu Zhou ◽  
Yu Zhang
Keyword(s):  
Myasthenia Gravis ◽  
Medical Center ◽  
Postoperative Radiotherapy ◽  
Clinical Manifestations ◽  
Subretinal Fluid ◽  
Metastatic Tumor ◽  
The Body ◽  
Pleural Thickening ◽  
History Of ◽  
Clinically Significant

Importance: This is the first reported case of acute exudative paraneoplastic polymorphous vitelliform maculopathy (AEPPVM) in a patient with thymoma, accompanied by myasthenia gravis (MG) and polymyositis. Objective: To examine the pathogenesis of ocular disease in a patient with yolk-like fundus lesions and thymoma, MG, and polymyositis throughout the body based on clinical manifestations, diagnosis, differential diagnosis, and genetic testing to determine the appropriate treatment course. Design, setting, and participants: We describe a 63-year-old woman who presented to our tertiary medical center with a 3-month history of reduced visual acuity in both eyes. Concurrent fundoscopy revealed a 2.0 × 1.7-mm, unifocal, yellow, round vitelliform lesion in the macular region, surrounded by multifocal, shallow, yellow-white pockets of subretinal fluid. The patient’s medical history included thymoma with thymectomy treatment, combined with pericardiectomy and postoperative radiotherapy (20 years prior), followed by a diagnosis of MG with suspect thymic association (15 years prior). Three years prior, the patient had been diagnosed with polymyositis related to paraneoplastic syndrome; 1 year prior, she had been examined for pleural thickening due to suspected metastatic tumor. Results: On her most recent follow-up visit at 3 months after initial diagnosis, the patient was stable with no clinically significant progression in ocular or systemic conditions.

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