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Autoimmunity Apr 2024Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some...
Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some patients with thymoma develop MG and others do not. In this study, we conducted a comparative phenotype analysis of thymocytes in type B thymomas in patients with MG (MG (+) thymomas) and without MG (MG (-) thymomas) fluorescence-activated cell sorting (FACS). Our results show that the developmental stages defined by the expression of CD3, CD4, and CD8 were largely maintained in both MG (+) and MG (-) thymomas, with CD4CD8 cells constituting the majority of thymocytes in type B thymoma, and no significant difference between this cell population was observed in MG (+) and MG (-) thymomas.We discovered that CD4CD8 thymocytes in MG (+) thymomas expressed low levels of αβ TCR and high levels of IL-7 receptor α (IL-7Rα), whereas in MG (-) thymomas, CD4CD8 thymocytes exhibited the opposite pattern of αβ TCR and IL-7Rα expression. These results suggest that the positive and negative selection processes of CD4CD8 thymocytes might differ between MG (+) thymomas and MG (-) thymomas. The expression of the Helios transcription factor is induced during negative selection and marks a group of T cells that have undergone negative selection and are likely to be deleted due to strong TCR binding with self-peptides/MHC ligands. We observed that the percentage of Helios-positive CD4SP T cells was greater in MG (-) than in MG (+) thymomas. Thus, the differentially regulated selection process of CD4CD8 thymocytes, which involves TCR and IL-7/IL-7Rα signaling, is associated with the presence of MG in type B thymomas.
Topics: Humans; Thymoma; Myasthenia Gravis; Receptors, Antigen, T-Cell, alpha-beta; Male; Thymocytes; Female; Middle Aged; Receptors, Interleukin-7; Adult; Aged; Thymus Neoplasms; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunophenotyping
PubMed: 38723105
DOI: 10.1080/08916934.2024.2347379 -
Frontiers in Microbiology 2024Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them...
BACKGROUND
Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established.
METHODS
From the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done.
RESULTS
We discovered that a higher relative abundance of the genus (OR: 1.213, 95% CI: 1.006-1.462, = 0.043, P = 0.048) and the genus (OR: 1.255, 95% CI: 1.012-1.556, = 0.038, P = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class (OR: 3.016, 95% CI: 1.228-7.411, = 0.016, P = 0.021), the genus (OR: 2.787, 95% CI: 1.140-6.816, = 0.025, P = 0.025), and the phylum (OR: 3.016, 95% CI: 1.228-7.411, = 0.016, P = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus (OR: 2.450, 95% CI: 1.072-5.598, = 0.034, P = 0.036), the genus (OR: 2.437, 95% CI: 1.215-4.888, = 0.012, P = 0.024), genus (OR: 3.681, 95% CI: 1.288-10.521, = 0.015, P = 0.025) and the genus (OR: 2.157, 95% CI: 1.211-3.843, = 0.003, P = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality.
CONCLUSION
Our findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.
PubMed: 38721606
DOI: 10.3389/fmicb.2024.1337632 -
Clinical Case Reports May 2024Neuromyelitis optica spectrum disorder is an autoimmune disease, rarely presents with antiphospholipid syndrome. Diagnosis and management of NMOSD are challenging in the...
KEY CLINICAL MESSAGE
Neuromyelitis optica spectrum disorder is an autoimmune disease, rarely presents with antiphospholipid syndrome. Diagnosis and management of NMOSD are challenging in the background of diverse presentations, especially in resource-limited settings.
ABSTRACT
Neuromyelitis optica spectrum disorder (NMOSD) is a progressive demyelinating autoimmune condition resulting from the autoantibodies produced against aquaporin-4 (AQP-4) proteins which are widely distributed in astrocytes in the nervous system. In the setting of NMOSD, it is very crucial to consider other autoimmune diseases as differential diagnoses or co-occurrences due to the diversity of symptoms. NMOSD co-exists with other autoimmune diseases such as myasthenia gravis, thyroid disease, ankylosing spondylitis, pernicious anemia, thrombotic thrombocytopenic purpura, ulcerative colitis, and systemic lupus erythematosus. Few cases of antiphospholipid syndrome co-existing with NMOSD have been reported. In resource-limited settings, the published data are scarce, and therefore, autoimmune diseases are poorly studied. Therefore, late diagnosis and delayed treatment initiation pose long-term sequelae and hence poor prognosis. Here, we present a case of an African woman in her early 40s presenting with bilateral progressive loss of vision, transverse myelitis, extensive longitudinal hyperintense T2 cervical lesion, and AQP-4 autoantibody keeping with NMOSD. The co-existence of antiphospholipid syndrome, in this case, was supported by a history of recurrent pregnancy loss and positive antiphospholipid antibodies. This case underscores the importance of individualized-based medicine, especially in resource-limited settings.
PubMed: 38721556
DOI: 10.1002/ccr3.8818 -
Heliyon May 2024Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks...
INTRODUCTION
Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD.
CASE PRESENTATION
We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period.
CONCLUSION
As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.
PubMed: 38720715
DOI: 10.1016/j.heliyon.2024.e30421 -
Gland Surgery Apr 2024Myasthenic crisis (MC) may occur after thymectomy in patients with myasthenia gravis (MG), but effective preventive interventions can reduce the occurrence of this... (Review)
Review
BACKGROUND
Myasthenic crisis (MC) may occur after thymectomy in patients with myasthenia gravis (MG), but effective preventive interventions can reduce the occurrence of this complication. Previous research on MC focused on risk factors, emergency treatment, etc., which was relatively scattered and did not form a comprehensive management framework. This study sought to retrieve and summarize the relevant evidence on the prevention and management of postoperative MC to provide a theoretical reference for clinical medical staff.
METHODS
According to the evidence pyramid model, relevant articles were retrieved from UpToDate, British Medical Journal (BMJ) Best Practice, World Health Organization (WHO), Scottish Intercollegiate Guidelines Network (SIGN), Guidelines International Network (GIN), Australian Joanna Briggs Institute (JBI) Healthcare Database, Medlive, PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang. The types of evidence included clinical guidelines, expert consensus articles, clinical decisions, systematic reviews, and randomized controlled trials (RCTs). The quality evaluations were conducted using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) evaluation tool for guidelines, the Australian JBI Evidence-Based Healthcare Center evaluation tool for expert consensus articles, the Critical Appraisal for Summaries of Evidence (CASE) evaluation tool for clinical decisions, the Assessment of Multiple Systematic Reviews (AMSTAR) evaluation tool for systematic reviews, and the Cochrane risk-of-bias tool for RCTs.
RESULTS
A total of 12 articles were included in this study, including three clinical guidelines, three expert consensus articles, three clinical decisions, two systematic reviews, and one RCT. From these articles, we summarized 39 pieces of evidence on the prevention and management of postoperative MC.
CONCLUSIONS
This study summarized the best evidence on the prevention and management of postoperative MC and provided to clinical staffs evidence-based clinical approaches to help reduce the incidence of this complication.
PubMed: 38720682
DOI: 10.21037/gs-24-90 -
Internal Medicine (Tokyo, Japan) May 2024A man in his 80s with myasthenia gravis (MG) developed dysmobility and chest discomfort. An electrocardiogram revealed ST-segment elevation, and coronary angiography...
A man in his 80s with myasthenia gravis (MG) developed dysmobility and chest discomfort. An electrocardiogram revealed ST-segment elevation, and coronary angiography revealed Takotsubo syndrome (TTS). He experienced myasthenic crisis that required ventilation and shock that was refractory to vasopressors and required intra-aortic balloon pump (IABP) insertion. He was managed conservatively without MG-specific treatment until his hemodynamics improved. On hospital day 6, he was weaned from IABP. MG is a high-risk condition for TTS, and TTS with MC is associated with high mortality. We successfully managed this case of TTS with MC with intubation and IABP, without MG-specific treatment.
PubMed: 38719601
DOI: 10.2169/internalmedicine.3306-23 -
Frontiers in Immunology 2024Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of...
INTRODUCTION
Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied.
METHODS
We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17-79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2-82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20-68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry.
RESULTS
We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission.
DISCUSSION
We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.
Topics: Humans; Myasthenia Gravis; Male; Middle Aged; Female; Adult; Aged; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Immunoglobulin G; Retrospective Studies; Young Adult; Adolescent; Autoantibodies; Aged, 80 and over; Immunosuppression Therapy; Immunosuppressive Agents; Severity of Illness Index; Child
PubMed: 38715598
DOI: 10.3389/fimmu.2024.1325171 -
International Journal of... 2024Cell metabolism functions without a stop in normal and pathological cells. Different metabolic changes occur in the disease. Cell metabolism influences biochemical and... (Review)
Review
BACKGROUND
Cell metabolism functions without a stop in normal and pathological cells. Different metabolic changes occur in the disease. Cell metabolism influences biochemical and metabolic processes, signaling pathways, and gene regulation. Knowledge regarding disease metabolism is limited.
OBJECTIVE
The review examines the cell metabolism of glucose, nucleotides, and lipids during homeostatic and pathological conditions of neurotoxicity, neuroimmunological disease, Parkinson's disease, thymoma in myasthenia gravis, and colorectal cancer.
METHODS
Data collection includes electronic databases, the National Center for Biotechnology Information, and Google Scholar, with several inclusion criteria: cell metabolism, glucose metabolism, nucleotide metabolism, and lipid metabolism in health and disease patients suffering from neurotoxicity, neuroinflammation, Parkinson's disease, thymoma in myasthenia gravis. The initial number of collected and analyzed papers is 250. The final analysis included 150 studies out of 94 selected papers. After the selection process, 62.67% remains useful.
RESULTS AND CONCLUSION
A literature search shows that signaling molecules are involved in metabolic changes in cells. Differences between cancer and neuroimmunological diseases are present in the result section. Our finding enables insight into novel therapeutic targets and the development of scientific approaches for cancer and neurological disease onset, outcome, progression, and treatment, highlighting the importance of metabolic dysregulation. Current understanding, emerging research technologies and potential therapeutic interventions in metabolic programming is disucussed and highlighted.
Topics: Humans; Lipid Metabolism; Neoplasms; Nervous System Diseases; Nucleotides; Glucose; Animals; Signal Transduction
PubMed: 38712748
DOI: 10.1177/03946320241250293 -
Frontiers in Immunology 2024Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and...
Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear. Thus, in this study, we aimed to elucidate the pathogenic mechanism of seronegative MG using scRNA-seq analysis and plasma proteome analysis; in particular, we investigated the relationship between immune dysregulation status and disease severity in refractory seronegative MG. Employing single-cell RNA-sequencing and plasma proteome analyses, we analyzed peripheral blood samples from 30 women divided into three groups: 10 healthy controls, 10 early-onset AChR-positive MG, and 10 refractory early-onset seronegative MG patients, both before and after intravenous immunoglobulin treatment. The disease severity was evaluated using the MG-Activities of Daily Living (ADL), MG composite (MGC), and revised 15-item MG-Quality of Life (QOL) scales. We observed numerical abnormalities in multiple immune cells, particularly B cells, in patients with refractory seronegative MG, correlating with disease activity. Notably, severe MG cases had fewer regulatory T cells without functional abnormalities. Memory B cells were found to be enriched in peripheral blood cells compared with naïve B cells. Moreover, plasma proteome analysis indicated significantly lower plasma protein levels of soluble CD22, expressed in the lineage of B-cell maturation (including mature B cells and memory B cells), in refractory seronegative MG patients than in healthy donors or patients with AChR-positive MG. Soluble CD22 levels were correlated with disease severity, B-cell frequency, and RNA expression levels of CD22. In summary, this study elucidates the immunopathology of refractory seronegative MG, highlighting immune disorders centered on B cells and diminished soluble CD22 levels. These insights pave the way for novel MG treatment strategies focused on B-cell biology.
Topics: Humans; Myasthenia Gravis; Female; Adult; B-Lymphocytes; Sialic Acid Binding Ig-like Lectin 2; Middle Aged; Autoantibodies; Immunoglobulins, Intravenous; Receptors, Cholinergic; Severity of Illness Index; Young Adult; Proteome
PubMed: 38711503
DOI: 10.3389/fimmu.2024.1382320 -
Heliyon May 2024Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed...
Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.
PubMed: 38707411
DOI: 10.1016/j.heliyon.2024.e30015