-
Frontiers in Immunology 2020
Topics: Animals; Autoantibodies; Autoimmunity; Humans; Immunosuppressive Agents; LDL-Receptor Related Proteins; Myasthenia Gravis; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic
PubMed: 32983085
DOI: 10.3389/fimmu.2020.01688 -
Frontiers in Neurology 2022
PubMed: 36188382
DOI: 10.3389/fneur.2022.1025183 -
Brain and Behavior Nov 2023Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic...
BACKGROUND
Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic correlation and causal relationship between COVID-19 susceptibility, hospitalization, severity, and MG phenotypes using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) approach.
METHODS
Summary statistics of COVID-19 susceptibility, hospitalization, and severity were used as instrumental variables for exposure traits. Large-scale genome-wide association study (GWAS) data for MG were used as outcome traits. The inverse variance weighted approach was used for the main MR analysis, complemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analysis was implemented using Cochran's Q test, MR-PRESSO method, and MR-Egger intercept test.
RESULTS
LDSC analysis did not reveal any genetic correlation among COVID-19 susceptibility, hospitalization, severity, and MG phenotypes, including MG, early-onset MG, and late-onset MG (p > .05). Our MR analysis did not provide evidence supporting a causal effect of COVID-19 susceptibility, hospitalization, or severity on MG phenotypes (p > .05). Extensive sensitivity analysis strengthened the robustness and consistency of the MR estimates.
CONCLUSION
Our study did not find evidence of a genetic correlation or causal relationship among COVID-19 susceptibility, hospitalization, severity, and MG. Future studies with more GWAS data are needed to evaluate the association between COVID-19 phenotypes and MG and its subgroups.
Topics: Humans; COVID-19; Genome-Wide Association Study; Mendelian Randomization Analysis; Hospitalization; Myasthenia Gravis
PubMed: 37638499
DOI: 10.1002/brb3.3239 -
European Journal of Case Reports in... 2021Myasthenia gravis is a rare autoimmune disease caused by autoantibodies directed against the synapses of the neuromuscular junction.
INTRODUCTION
Myasthenia gravis is a rare autoimmune disease caused by autoantibodies directed against the synapses of the neuromuscular junction.
PATIENT AND METHODS
We report the case of a young patient with myasthenia gravis associated with Hodgkin's lymphoma.
RESULTS
A 22-year-old patient presented with a 2-month history of severe weakness associated with muscle fatigability and intermittent ptosis without dysphonia or respiratory signs. Clinical examination revealed generalized myasthenia. The EMG did not show post-synaptic block, and anti-acetylcholine receptor antibodies were elevated at 3 nmol/l (normal ≤0.3 nmol/l). CT of the thorax showed an anterior medial mass. Immunohistochemistry of the mass revealed mixed cellularity Hodgkin's lymphoma.
CONCLUSION
The association of lymphomas with myasthenia gravis has been rarely reported.
LEARNING POINTS
Myasthenia gravis is an autoimmune disease of the neuromuscular junction and can be associated with malignant haemopathy.The coexistence of myasthenia and Hodgkin's lymphoma is very rare.This association is a therapeutic challenge.
PubMed: 33987113
DOI: 10.12890/2021_002375 -
Acta Neuropathologica Jun 2021Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although...
Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature Th and Th cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment.
Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmunity; B-Lymphocytes; Biomarkers; Female; Humans; Immunophenotyping; Machine Learning; Male; Middle Aged; Myasthenia Gravis; Receptors, Cholinergic; Single-Cell Analysis; T-Lymphocytes; Thymectomy; Thymus Gland
PubMed: 33774709
DOI: 10.1007/s00401-021-02299-y -
Neurologia 2023
Topics: Humans; Vitamin D; Myasthenia Gravis
PubMed: 36462625
DOI: 10.1016/j.nrleng.2021.11.006 -
Frontiers in Immunology 2020Complement activation as a driver of pathology in myasthenia gravis (MG) has been appreciated for decades. The terminal complement component [membrane attack complex... (Review)
Review
Complement activation as a driver of pathology in myasthenia gravis (MG) has been appreciated for decades. The terminal complement component [membrane attack complex (MAC)] is found at the neuromuscular junctions of patients with MG. Animals with experimental autoimmune MG are dependent predominantly on an active complement system to develop weakness. Mice deficient in intrinsic complement regulatory proteins demonstrate a significant increase in the destruction of the neuromuscular junction. As subtypes of MG have been better defined, it has been appreciated that acetylcholine receptor antibody-positive disease is driven by complement activation. Preclinical assessments have confirmed that complement inhibition would be a viable therapeutic approach. Eculizumab, an antibody directed toward the C5 component of complement, was demonstrated to be effective in a Phase 3 trial with subsequent approval by the Federal Drug Administration of the United States and other worldwide regulatory agencies for its use in acetylcholine receptor antibody-positive MG. Second- and third-generation complement inhibitors are in development and approaching pivotal efficacy evaluations. This review will summarize the history and present the state of knowledge of this new therapeutic modality.
Topics: Animals; Antibodies, Monoclonal, Humanized; Complement Activation; Complement C5; Complement Inactivating Agents; Disease Models, Animal; Humans; Myasthenia Gravis; Treatment Outcome
PubMed: 32582144
DOI: 10.3389/fimmu.2020.00917 -
Cleveland Clinic Journal of Medicine Feb 2023
Topics: Humans; Myasthenia Gravis; Physicians
PubMed: 36724915
DOI: 10.3949/ccjm.90b.02023 -
Heliyon Jun 2023The purpose of this study was to investigate the epidemiology, management, and economic burden of myasthenia gravis in settings of real clinical practice. The analysis...
The purpose of this study was to investigate the epidemiology, management, and economic burden of myasthenia gravis in settings of real clinical practice. The analysis used administrative databases covering around 12 million subjects across Italy and included all adult patients with hospitalization discharge diagnosis or active exemption code for myasthenia gravis or with ≥1 pyridostigmine prescription from 2011 to 2018. The estimated prevalence of myasthenia gravis during 2018 was in the range 13.5-29.3/100,000 people (depending on the criteria applied), corresponding to 8190-17,728 alive patients, when reproportioning data to the entire Italian population. Overall 4397 patients with myasthenia gravis (mean age 61.7 years, 46.6% males) were included. A large pyridostigmine use was observed (84.0%-46.8% from 1st to 3rd year of follow-up), followed by corticosteroids (54.5%-44.6% from 1st to 3rd year of follow-up) and non-steroidal immunosuppressants (16% over follow-up). Total direct healthcare costs for myasthenia gravis were 4-times higher than those of the general population (€3771 and €869, respectively), and up to 9-fold increased when considering patients with exacerbation (€7827). These findings showed the epidemiologic burden of myasthenia gravis and the complexity of the therapeutic management for the affected patients, with large use of treatments and elevated healthcare expenditures.
PubMed: 37274644
DOI: 10.1016/j.heliyon.2023.e16367 -
European Respiratory Review : An... Dec 2021Thymic tumours are rare thoracic malignancies, that may be aggressive and difficult to treat. The pillars of the management include pathological review, consideration of... (Review)
Review
Thymic tumours are rare thoracic malignancies, that may be aggressive and difficult to treat. The pillars of the management include pathological review, consideration of differential diagnoses, staging and multidisciplinary discussion. Assessment of resectability is key to drive the treatment sequencing. Association with autoimmune diseases, especially myasthenia gravis, is observed, which impacts the oncological management. Networks are being built at the national and international levels. This article provides an overview of the most recent findings in the diagnosis, staging, histology, and management strategies of thymic tumours.
Topics: Diagnosis, Differential; Humans; Myasthenia Gravis; Retrospective Studies; Thymoma; Thymus Neoplasms
PubMed: 34670805
DOI: 10.1183/16000617.0394-2020