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Frontiers in Neurology 2024Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components...
Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG.
PubMed: 38751878
DOI: 10.3389/fneur.2024.1356300 -
Therapeutic Advances in Neurological... 2024Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody...
BACKGROUND
Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition.
OBJECTIVES
This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG.
DESIGN
A single-center retrospective study.
METHODS
Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated.
RESULTS
Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups ( < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months ( < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported.
CONCLUSION
Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.
PubMed: 38751755
DOI: 10.1177/17562864241251476 -
Journal of Korean Medical Science May 2024During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness...
BACKGROUND
During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea.
METHODS
This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients.
RESULTS
Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized ( < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients ( = 0.019 and = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients ( = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients.
CONCLUSION
This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
Topics: Humans; COVID-19; Myasthenia Gravis; Retrospective Studies; Male; Female; Middle Aged; Republic of Korea; Aged; SARS-CoV-2; Adult; COVID-19 Vaccines; Hospitalization; Vaccination; Prognosis; Intensive Care Units; Respiration, Artificial
PubMed: 38742290
DOI: 10.3346/jkms.2024.39.e150 -
CNS Neuroscience & Therapeutics May 2024This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab.
BACKGROUND
This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab.
METHODS
We retrospectively reviewed 108 patients who received rituximab of 600 mg every 6 months in Huashan Hospital and Tangdu Hospital. Of them, 76 patients from Huashan Hospital were included in the derivation cohort to develop the predictive nomogram, which was externally validated using 32 patients from Tangdu Hospital. The clinical response is defined as a ≥ 3 points decrease in QMG score within 6 months. Both clinical and genetic characteristics were included to screen predictors via multivariate logistic regression. Discrimination and calibration were measured by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively.
RESULTS
Disease duration (OR = 0.987, p = 0.032), positive anti-muscle-specific tyrosine kinase antibodies (OR = 19.8, p = 0.007), and genotypes in FCGR2A rs1801274 (AG: OR = 0.131, p = 0.024;GG:OR = 0.037, p = 0.010) were independently associated with clinical response of post-rituximab patients. The nomogram identified MG patients with clinical response with an AUC-ROC (95% CI) of 0.875 (0.798-0.952) in the derivation cohort and 0.741(0.501-0.982) in the validation cohort. Hosmer-Lemeshow test showed a good calibration (derivation: Chi-square = 3.181, p = 0.923; validation: Chi-square = 8.098, p = 0.424).
CONCLUSIONS
The nomogram achieved an optimal prediction of short-term outcomes in patients treated with low-dose rituximab.
Topics: Humans; Rituximab; Myasthenia Gravis; Male; Female; Middle Aged; Nomograms; Adult; Retrospective Studies; Immunologic Factors; Treatment Outcome; Aged; Young Adult; Receptors, IgG
PubMed: 38739094
DOI: 10.1111/cns.14761 -
Mediterranean Journal of Rheumatology Mar 2024Various muscles can be involved in idiopathic eosinophilic myositis (IEM), with the ocular muscles being notably affected. Ocular eosinophilic myositis is a rare...
Various muscles can be involved in idiopathic eosinophilic myositis (IEM), with the ocular muscles being notably affected. Ocular eosinophilic myositis is a rare condition that typically affects the rectus muscles. A tissue biopsy stands as the gold standard for diagnosis. Different subtypes exist based on the extent of eosinophilic infiltration. Limited data is available about treatment, although glucocorticoids have shown successful outcomes. We present the case of a 60-year-old man who, a few years after being diagnosed with ocular myasthenia gravis, was diagnosed through a tissue biopsy with ocular eosinophilic myositis. Treatment with oral glucocorticoids significantly improved his symptoms.
PubMed: 38736949
DOI: 10.31138/mjr.150523.eom -
Journal of Neuroinflammation May 2024Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T...
Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.
Topics: Myasthenia Gravis; Thymoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; T-Lymphocytes, Regulatory; Th17 Cells; Thymus Gland; Male; Female; Thymus Neoplasms; Adult; Middle Aged; Aged
PubMed: 38734662
DOI: 10.1186/s12974-024-03095-7 -
Indian Journal of Pathology &... May 2024Myasthenia gravis is an autoimmune disorder caused by the formation of autoantibodies directed against the synapses of neuromuscular junction. It is most commonly...
Myasthenia gravis is an autoimmune disorder caused by the formation of autoantibodies directed against the synapses of neuromuscular junction. It is most commonly associated with other non-thymomatous lesions. Castleman disease is one of them, which is a benign lymphoproliferative disorder of uncertain origin. Only eight cases of myasthenia gravis associated with Castleman disease have been described so far. Here, we take the opportunity to describe a case of myasthenia gravis with Castleman disease simulating thymoma clinically and radiologically along with review of literature of this rare association. Patient developed myasthenic crisis in the immediate post-operative period which is more common in myasthenia gravis with Castleman disease rather than myasthenia gravis with thymoma.
PubMed: 38727419
DOI: 10.4103/ijpm.ijpm_482_23 -
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