Figure - available from: Frontiers in Neurology
This content is subject to copyright.
Curation of records. Papers captured by search algorithms in PubMed and Web of Science (n = 827) were manually curated to remove duplicates (n = 592). Papers were screened to assess whether they met the inclusion and exclusion criteria, yielding a total of 48 publications. An additional 6 papers were retrieved from the reference lists of relevant articles.

Curation of records. Papers captured by search algorithms in PubMed and Web of Science (n = 827) were manually curated to remove duplicates (n = 592). Papers were screened to assess whether they met the inclusion and exclusion criteria, yielding a total of 48 publications. An additional 6 papers were retrieved from the reference lists of relevant articles.

Source publication
Article
Full-text available
Background: Myasthenia gravis (MG) is an autoimmune disorder of unknown etiology in most patients, in which autoantibodies target components of neuromuscular junctions and impair nerve to muscle transmission. Objective: To provide a synthesis of the evidence examining infectious agents associated with the onset of MG. Hypothesis: We hypothesized th...

Similar publications

Article
Full-text available
The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic diso...

Citations

... Myasthenia gravis (MG) is caused by antibodies (Abs) targeting proteins at the neuromuscular junction and thus resulting in J o u r n a l P r e -p r o o f Journal Pre-proof abnormal muscle fatigability [1]. Various environmental factors have been proposed to play a role in the pathogenesis of MG including infections [2], vaccinations 3, low serum levels of vitamin D [4], and smoking [5]. These factors exhibit seasonal variability that may impact MG onset and exacerbations. ...
... Viral infection can usually exacerbate myasthenia gravis, highlighting the vital role of the THαβ immunological pathway in disease pathogenesis. EBV, parvovirus, and HSV infections have been reported to be associated with the pathogenesis of myasthenia gravis [88,89]. Chemokine receptors and their ligands CXCR3 and IP10, which are related to THαβ immunity, are overexpressed in T lymphocytes in myasthenia gravis [90]. ...
Article
Full-text available
The THαβ host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαβ immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαβ host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves’ disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren’s syndrome have also been linked to the THαβ pathway. Considering the potential associations between these diseases and dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/β could be explored for effective management.
... Initial symptoms typically involve fatigue or muscle weakness, requiring an extensive examination. A blood test confirms the diagnosis by detecting antibodies against either MuSK or AChR [49], which are part of standard serological testing for MG. AChR antibodies are tested initially due to their high incidence in MG, followed by MuSK antibodies if the initial results are negative. ...
Article
Full-text available
Purpose of Review The aim is to elucidate the mechanisms of autoimmune dysregulation that contribute to the onset and course of Guillain–Barre Syndrome (GBS) and Myasthenia Gravis (MG), with an emphasis on the important role that the Epstein-Barr virus (EBV) plays as an exacerbator or trigger of these autoimmune reactions. It further explores diagnostic strategies and therapeutic approaches to improve patient outcomes. Recent Findings Recent researches have underscored the challenging nature of EBV due to its insidious behavior and persistent latency, which make it difficult to create successful preventive and therapeutic approaches. These discoveries have revealed how EBV's ability to induce host immune dysfunction can exacerbate or spark inflammatory processes, leading to its association with various autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sjögren's syndrome. Moreover, this review will shed light on the intricate connections between EBV and autoimmune neuromuscular disorders like MG and GBS, emphasizing the urgent requirement for further investigation to devise effective strategies against EBV-related conditions. Summary MG and GBS, while both autoimmune illnesses affecting the neuromuscular system, differ greatly in their pathogenesis and clinical presentation. Viral infections, notably EBV, are vital in causing or aggravating these diseases. Understanding the link between EBV and autoimmune dysregulation could enhance diagnostic accuracy, therapeutic approaches, and preventive options, such as antiviral medications or vaccinations. Continued research and interdisciplinary collaboration are crucial to clarify how EBV affects MG and GBS, potentially leading to tailored treatments. Identifying precise biomarkers and pathways will improve clinical protocols, public health standards, and education on the EBV-autoimmunity relationship.
... It is almost entirely characterized by ocular symptoms such as ptosis and diplopia and can progress to generalized myasthenia gravis (GMG) in about 20-60% of cases. 4,7 Myasthenia Gravis can be triggered by various factors, including drugs 8 , wasp stings 9 , neuroborreliosis 10 and HIV infection 11 . It can also develop following trauma such as a minor head injury and has also been reported to develop after cardiac surgery. ...
Article
Full-text available
We present here a 12-year-old child who presented with complaints of blurring of vision and drooping of the left upper eyelid for the past 4 years, which started 1 month after he encountered blunt trauma to the left-sided orbital region. History, examination and pharmacological (neostigmine test) tests were suggestive of ocular myasthenia gravis, however anti-acetylcholine receptor antibodies and anti-musk antibodies were negative. Repetitive nerve stimulation tests and electromyography were also unremarkable. The patient was labelled as a case of trauma-induced double-Seronegative Ocular Myasthenia Gravis and was started on oral Pyridostigmine. The patient reported a drastic improvement in both diplopia and ptosis that he initially presented with. Ocular Myasthenia Gravis can be a diagnostic challenge as its initial presentation can vary to a great degree. Thorough history and examination remain of prime importance which can provide adequate clues to lead us to the diagnosis of ocular myasthenia gravis. Trauma should also be recognized as a triggering factor for myasthenia gravis and more attention needs to be given to understand the pathophysiology of this interesting association.
... Contradictory studies exist for the presence of Epstein-Barr virus existence in the MG thymus (84,85). No evidence suggests other infectious agents to be associated with MG (86). Release of double-stranded DNA from necrotic macrophages may trigger the inflammatory and subsequent autoimmune reaction in the hyperplastic thymus (74). ...
Article
Full-text available
Myasthenia gravis (MG) stands as a prototypical antibody-mediated autoimmune disease: it is dependent on T cells and characterized by the presence of autoantibodies targeting proteins located on the postsynaptic surface of skeletal muscle, known as the neuromuscular junction. Patients with MG exhibit a spectrum of weakness, ranging from limited ocular muscle involvement to life-threatening respiratory failure. Recent decades have witnessed substantial progress in understanding the underlying pathophysiology, leading to the delineation of distinct subcategories within MG, including MG linked to AChR or MuSK antibodies as well as age-based distinction, thymoma-associated, and immune checkpoint inhibitor-induced MG. This heightened understanding has paved the way for the development of more precise and targeted therapeutic interventions. Notably, the FDA has recently approved therapeutic inhibitors of complement and the IgG receptor FcRn, a testament to our improved comprehension of autoantibody effector mechanisms in MG. In this Review, we delve into the various subgroups of MG, stratified by age, autoantibody type, and histology of the thymus with neoplasms. Furthermore, we explore both current and potential emerging therapeutic strategies, shedding light on the evolving landscape of MG treatment.
... Virus infection can usually cause the exacerbation of Myasthenia gravis, and this also pointed out the vital role of THαβ immunological pathway in the disease pathogenesis. EBV, parvovirus, and HSV infections have been reported to be associated with the pathogenesis of Myasthenia gravis [78,79]. Chemokine receptor and its ligand, CXCR3 and IP10, which are related to THαβ immunity, are overexpressed in T lymphocytes in Myasthenia gravis [80]. ...
Preprint
Full-text available
Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.
... Trigger factors for dysfunction of the neuroendocrine-immune complex in myasthenia gravis can be exogenous stress factors, bacterial and viral infections in target organs, including the thymus, which change the activity of body cells and contribute to the development of long-term inflammation due to the presence of persister cells [27,28]. ...
Chapter
Full-text available
The urgency of the problem is determined by the increasing prevalence and rapid progression of autoimmune diseases and autoimmune components in various nosologies. The aim is to study individual trigger factors, predictors of development, and the condition severity markers to substantiate complex treatment, including surgical tactics and the therapeutic target choice, in case of the immunocompetent organs (thymus and spleen) damage. In patients with myasthenia gravis the trigger markers were identified: the presence of herpes viruses persistence and mycoplasma; the relationship of certain human leucocyte antigen (HLA) molecules; high content of cytotoxic damage-associated molecular patterns (DAMPs); decreased expression of CD8+ T lymphocytes and co-stimulatory molecules CD3+CD4+CD28+. Some patients with myasthenia gravis had antibodies to α1 and α7 subunits nicotinic acetylcholine receptors (nAChR), etc. Patients with hepatosplenomegaly depending on the trigger factors (hepatitis HBV/HBC, herpes viruses (CMV/EBV)) and genetic predictors (hereditary enzymopathy) had specific markers, such as activation or inhibition of barrier function, reactive oxygen species (ROS) production, an increase in the concentration of cytokines, changes in the clusters of differentiation expression and specific autoantibodies. Thus, the creation of supplemented diagnostic protocols with additional markers for patients with various autoimmune reactions will make it possible to substantiate personalized immunocorrection.
... Studies have suggested that active EBV replication may play a pathogenic role in NMOSD [20], as elevated levels of IgG antibodies to the early antigen were detected in a cohort of Japanese patients with NMO compared to MS and healthy controls (HCs) [20]. Interestingly, EBV has also been linked to several autoimmune disease associated with NMOSD [21], such as myasthenia gravis [22], systemic lupus erythematosus [23], and Sjogren's syndrome [24]. Various hypotheses surround this connection: EBV may induce molecular mimicry, where viral antigens resemble self-antigens, contributing to the development or exacerbation of the disease. ...
Article
Full-text available
Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocytes glycoprotein-antibody disease (MOGAD) are distinct autoimmune demyelinating disorders characterized by varying clinical and pathological characteristics. While the precise origins of these diseases remain elusive, a combination of genetic and environmental factors, including viral elements, have been suggested as potential contributors to their development. Our goal was to assess the occurrence of antibodies against pathogenic peptides associated with Epstein–Barr virus (EBV) and the human endogenous retrovirus-W (HERV-W) in serum samples obtained from Japanese individuals diagnosed with MS, NMOSD, and MOGAD and to make comparisons with a group of healthy controls (HCs). We conducted a retrospective analysis involving 114 Japanese participants, comprising individuals with MS (34), NMOSD (20), MOGAD (20), and HCs (40). These individuals were tested using a peptide-based enzyme-linked immunosorbent assay. A marked increase in antibody response against EBV nuclear antigen 1 (EBNA1)386–405 was observed in the serum of MS and MOGAD patients, as compared to HCs. Notably, we observed a correlation between antibodies against EBNA1386–405 and HERV-W486–504 peptides in a subset of the antibody-positive MS patients. These findings emphasize the involvement of EBV in the pathogenesis of MS and potentially MOGAD, suggesting its role in the reactivation of HERV-W.
... Myasthenia gravis (MG) is one of the major autoimmune neuromuscular disorders [1]. Acetylcholine receptor (AChR) antibodies, which are the major specific autoantibodies detected in around 30% to 50% of patients with ocular MG (OMG) and 85% of patients with generalized MG (GMG), lead to tissue and functional damage at the neuromuscular junction [2][3][4][5]. On the other hand, 4% to 7% of all MG cases are associated with muscle specific kinase (MuSK) antibodies [1,5,6]. ...
... Some researches have reported that higher MGFA class, the absence of AChR antibodies, certain comorbidities and infections, or inappropriate therapeutic strategies can be potential predictors for an exacerbation of MC [4,9]. Some studies otherwise focused on the prognostic factors of MC among MG patients with thymectomy or not [9,14]. ...
... Consistent with previous studies, patients with thymic cancer tended to have more frequent infections, especially of the respiratory tract, contributing to an increased level of inflammatory cytokines [22,23]. About 10% to 15% of MG patients had thymoma, particular in those seropositivity group of AChR antibodies [1,4,8,22]. Thymoma-induced immune dysregulation and loss of self-tolerance not only provided a primary source of AChR antibodies but also reduced the systemic defenses against pathogens [3,6,22]. ...
Article
Full-text available
Background Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. Methods This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. Results The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. Conclusions The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.
... Chronic inflammation in the thymus due to persistent microbial infection has been reported to occur in MG patients (20). Disruption of tolerance and generation of autoreactive cells in the thymus are seemingly the first step for AChR-MG pathogenesis. ...
Article
Full-text available
Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is caused primarily by the binding of an autoantibody to the acetylcholine receptors, resulting in blockage of normal neuromuscular signal transmission. Studies revealed substantial contributions of different proinflammatory or inflammatory mediators in the pathogenesis of MG. Despite these findings, compared to therapeutic approaches that target autoantibody and complements, only a few therapeutics against key inflammatory molecules have been designed or tested in MG clinical trials. Recent research focuses largely on identifying unknown molecular pathways and novel targets involved in inflammation associated with MG. A well-designed combination or adjunct treatment utilizing one or more selective and validated promising biomarkers of inflammation as a component of targeted therapy may yield better treatment outcomes. This review briefly discusses some preclinical and clinical findings of inflammation associated with MG and current therapy approaches and suggest the potential of targeting important inflammatory marker(s) along with current monoclonal antibody or antibody fragment based targeted therapies directed to a variety of cell surface receptors.