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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
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
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
... 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). ...
... 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]. ...
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]. ...
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. ...
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]. ...
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. ...
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.
... In MG, the transmission of nerve impulses to the muscles is disrupted. When there is no nervemuscle connection, muscles are disrupted and cause neuromuscular disorders in these patients (Leopardi et al., 2021). ...
Objective
Myasthenia gravis (MG) people experience adverse psychiatric outcomes, which may impact on their life and disturb their daily activity. Depression and anxiety are identified as significant psychiatric problems that MG people face. However, there is no sufficient epidemiological information about depression and anxiety‐based publication. Due to this limitation, the aim of this study was to review the prevalence of depression and anxiety in MG patients.
Methods
Original and international databases were searched to find papers about the estimation of anxiety and depression. Random‐effects analysis was used for calculating the proportions of anxiety and depression. For estimating anxiety and depression based the severity, instruments, type of studies, and study regions, subgroup analysis was performed.
Results
38 studies met inclusion criteria and entered study. The pooling of the prevalence of depression was found at 36%, (95% CI 28% to 45%). Also, prevalence of anxiety was found at 33%, (95% CI 25% to 42%). Prevalence of depression based on mild, moderate, and severe level was 27%, 14%, and 9%, respectively.
Conclusions
Anxiety and depression are a major concern among MG individuals. The estimation of both anxiety and depression are high even when compared to other autoimmune diseases. It seems depression and anxiety are important issues and more attention needs to be paid to these psychiatric disorders.
... Rarely, MG onset can be triggered or worsened by infectious diseases [1] but this topic is still a matter of debate [2]. ...
Background: Myasthenia gravis (MG) is an autoimmune disease that targets acetylcholine receptor (AChR) of the neuro-muscular junction. New-onset MG after SARS-CoV-2 vaccination has rarely been reported.
Case presentation: We report about three patients who presented new-onset myasthenia gravis after receiving mRNA SARS-CoV-2 vaccination. The patients were all males and older than 55 years. All the patients presented with ocular and bulbar symptoms. The interval between vaccine administration and MG onset ranged from 3 days after the first dose to 10 days after the second dose. All the patients had elevated serum AChR antibodies and responded to pyridostigmine. Two out of three patients were successfully treated with IVIG or plasma exchange and with long-term immunosuppression.
Conclusions: MG is a rare disease; clinicians should be aware of possible new-onset MG after SARS-CoV-2 vaccination, especially with the current recommendation of booster doses. The hyperstimulation of the innate immune system or the exacerbation of a subclinical pre-existing MG could be possible explanations.
... Several mechanisms have been postulated to explain how pathogen infections might trigger autoimmunity: molecular mimicry or bystander effect [105]. The implication of viral infection in the triggering of MG is greatly debated [106]. As for other autoimmune diseases such as SLE, multiple sclerosis, and rheumatoid arthritis [107], several studies have investigated the potential link between MG and Epstein-Barr virus (EBV). ...
... To conclude, Leopardi et al. recently compile all the scientific publications referring to infectious agents. So far, there is no clear evidence that a specific pathogen infection causes MG [106]. ...
Myasthenia gravis (MG) is a rare autoimmune disease mediated by antibodies against components of the neuromuscular junction, particularly the acetylcholine receptor (AChR). The thymus plays a primary role in AChR-MG patients. In early-onset AChR-MG and thymoma-associated MG, an interferon type I (IFN-I) signature is clearly detected in the thymus. The origin of this chronic IFN-I expression in the thymus is not yet defined. IFN-I subtypes are normally produced in response to viral infection. However, genetic diseases called interferonopathies are associated with an aberrant chronic production of IFN-I defined as sterile inflammation. Some systemic autoimmune diseases also share common features with interferonopathies. This review aims to analyze the pathogenic role of IFN-I in these diseases as compared to AChR-MG in order to determine if AChR-MG could be an acquired interferonopathy.
... 38,39 Viral infections that induce IFN-I expression have long been suspected as myas thenia gravis triggers, but so far no specific pathogen has been linked. 40 Immunological dys regu lation is a clear hallmark of autoimmunity, but the exact trigger and progression factors in myasthenia gravis and Lambert-Eaton myasthenic syndrome are yet to be discovered. ...
Muscle weakness and fatigue are the hallmarks of autoimmune neuromuscular junction disorders. Although a plethora of immunosuppressive treatments exist, no cure is available to date and many patients are left with debilitating muscle weakness. Recent advances in the understanding of the structure and function of the neuromuscular junction, and the development of novel in vitro and in vivo models, have been instrumental in unravelling the pathophysiology of these autoimmune diseases. These advances are providing the rationale for the development of new therapeutic strategies. Restoration of the immune imbalance in these diseases, in parallel with symptomatic therapeutic approaches at the neuromuscular junction, will be crucial to obtain long-term remission or even cure.
