RESUMEN

Myasthenia gravis is an autoimmune disease characterized by muscle weakness and pathological fatigue due to autoaggressive phenomena with the formation of antibodies directed against various structures of the neuromuscular synapse. In most patients, the disease begins with the involvement of extraocular muscles, presenting with symptoms such as intermittent ptosis of the upper eyelid and/or binocular diplopia. In 15% of cases, clinical manifestations are limited to impairment of the levator palpebrae superioris and extraocular muscles, characteristic of the ocular form of myasthenia gravis. Specialists often encounter challenges in diagnosing this form, as serological and electrophysiological studies may be uninformative, necessitating diagnosis based on patient history and clinical picture. This literature review outlines the key aspects of the pathogenesis, clinical manifestations, methods of diagnosis and treatment of ocular myasthenia gravis.

Asunto(s)

Miastenia Gravis , Músculos Oculomotores , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatología , Miastenia Gravis/terapia , Miastenia Gravis/complicaciones , Humanos , Músculos Oculomotores/fisiopatología , Diagnóstico Diferencial

RESUMEN

The THαß 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 THαß 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 THαß 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 THαß pathway. Considering the potential associations between these diseases and dysregulated THαß immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/ß could be explored for effective management.

Asunto(s)

Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Sjögren/inmunología , Enfermedad Injerto contra Huésped/inmunología , Enfermedades Autoinmunes/inmunología , Citocinas/inmunología , Miastenia Gravis/inmunología , Anemia Hemolítica Autoinmune/inmunología , Enfermedad de Graves/inmunología , Enfermedad de Graves/complicaciones , Dermatomiositis/inmunología

RESUMEN

BACKGROUND: Myasthenia gravis is an autoimmune disease with high prevalence of thymus disorders, in which, thymectomy is considered one of the therapeutic approaches in improving the patients' clinical outcomes. Today, thoracoscopic thymectomy has received significant attention than the classic transsternal approach due to fewer complication. Therefore, this study was designed with the aim of investigating the therapeutic outcomes of thymectomy in patients with myasthenia gravis in the Afzalipour Hospital of Kerman between 2011 and 2021. METHODS: The current study is a descriptive analytical study on patients with myasthenia gravis who underwent surgical thymectomy within 2011-2021. Demographic and clinical characteristics of patients from the time of operation to three years of follow-up were extracted and recorded from clinical records or by phone calls. Data were analyzed using SPSS software. RESULTS: The data of 70 patients who underwent surgical thymectomy were analyzed. Thymectomy caused a significant reduction in the severity of the disease according to the Osserman classification (P = 0.001). It also significantly reduced the use of corticosteroids (P = 0.001) and IVIG (P = 0.015) compared to the time before the surgery. Sixty-two patients (88.57%) needed to take less medicine than before surgery. Left VATS was associated with less post-operative severity of the disease (P = 0.023). There were only two deaths during the follow-up period. CONCLUSION: Overall, the findings of the present study demonstrated that thoracoscopic thymectomy is a useful surgical approach that leads to faster recovery, reducing the severity of the disease, need for medication, and complications in patients with myasthenia gravis, In comparison with the transsternal approach.

Asunto(s)

Miastenia Gravis , Timectomía , Humanos , Miastenia Gravis/cirugía , Timectomía/métodos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Retrospectivos , Adulto Joven , Toracoscopía/métodos , Adolescente , Cirugía Torácica Asistida por Video/métodos , Estudios de Seguimiento

RESUMEN

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

Asunto(s)

COVID-19 , Miastenia Gravis , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Adulto , Factores de Riesgo , Anciano , Índice de Severidad de la Enfermedad , Comorbilidad

RESUMEN

BACKGROUND AND OBJECTIVES: In this retrospective longitudinal study, we aimed at exploring the role of (a) MuSK-immunoglobulin G (IgG) levels, (b) predominant MuSK-IgG subclasses, and (c) antibody affinity as candidate biomarkers of severity and outcomes in MuSK-MG, using and comparing different antibody testing techniques. METHODS: Total MuSK-IgGs were quantified with radioimmunoassay (RIA), ELISA, flow cytometry, and cell-based assay (CBA) serial dilutions using HEK293 cells transfected with MuSK-eGFP. MuSK-IgG subclasses were measured by flow cytometry. SAffCon assay was used for determining MuSK-IgG affinity. RESULTS: Forty-three serum samples were obtained at different time points from 20 patients with MuSK-MG (median age at onset: 48 years, interquartile range = 27.5-72.5; women, 16/20), with 9 of 20 (45%) treated with rituximab. A strong correlation between MuSK-IgG levels measured by flow cytometry and RIA titers was found (rs = 0.74, 95% CI 0.41-0.89, p = 0.0003), as well as a moderate correlation between CBA end-point titers and RIA titers (rs = 0.47, 95% CI 0.01-0.77, p = 0.0414). A significant correlation was found between MuSK-IgG flow cytometry levels and disease severity (rs = 0.39, 95% CI 0.06-0.64, p = 0.0175; mixed-effects model estimate: 2.296e-06, std. error: 1.024e-06, t = 2.243, p = 0.032). In individual patients, clinical improvement was associated with decrease in MuSK-IgG levels, as measured by either flow cytometry or CBA end-point titration. In all samples, MuSK-IgG4 was the most frequent isotype (mean ± SD: 90.95% ± 13.89). A significant reduction of MuSK-IgG4 and, to a lesser extent, of MuSK-IgG2, was seen in patients with favorable clinical outcomes. A similar trend was confirmed in the subgroup of rituximab-treated patients. In a single patient, MuSK-IgG affinity increased during symptom exacerbation (KD values: 62 nM vs 0.6 nM) while total MuSK-IgG and IgG4 levels remained stable, suggesting that affinity maturation may be a driver of clinical worsening. DISCUSSION: Our data support the quantification of MuSK antibodies by flow cytometry. Through a multimodal investigational approach, we showed that total MuSK-IgG levels, MuSK-IgG4 and MuSK-IgG2 levels, and MuSK-IgG affinity may represent promising biomarkers of disease outcomes in MuSK-MG.

Asunto(s)

Biomarcadores , Inmunoglobulina G , Miastenia Gravis , Receptores Colinérgicos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Miastenia Gravis/sangre , Miastenia Gravis/inmunología , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/diagnóstico , Adulto , Estudios Retrospectivos , Anciano , Inmunoglobulina G/sangre , Biomarcadores/sangre , Receptores Colinérgicos/inmunología , Estudios Longitudinales , Autoanticuerpos/sangre , Proteínas Tirosina Quinasas Receptoras/inmunología , Proteínas Tirosina Quinasas Receptoras/sangre , Células HEK293 , Rituximab/farmacología , Factores Inmunológicos/farmacología

RESUMEN

Acquired myasthenia (AM), a debilitating autoimmune disease, is typically characterized by skeletal muscle fatigue and weakness. Despite advances in myasthenia gravis treatment, current approaches remain unsatisfactory and many result in unexpected side effects. Traditional Chinese medicine has shown great potential in the treatment of myasthenia gravis, including relieving myasthenic symptoms, improving patients' quality of life, and reducing Western medicine side effects. This study investigates the protective effects and mechanism of BZYQD in mice with acquired myasthenia. BZYQD alleviates the reduced grip strength and increased expression of MAFbx and MuRF-1 in mice with acquired myasthenia. It also reduces levels of pro-inflammatory factors IL-1ß, IL-6, and TNF-α in the mouse serum. In addition, BZYQD reduces ROS accumulation and the mitochondrial ROS production rate, while increasing ATP levels and mitochondrial membrane potential in mice with acquired myasthenia. Moreover, BZYQD decreases the expression of p-JAK2, p-STAT3, and p-AKT in the skeletal muscle of mice with acquired myasthenia. In summary, BZYQD reduces inflammation, enhances mitochondrial function, and regulates the JAK2/STAT3/AKT signaling pathway to treat acquired myasthenia.

Asunto(s)

Medicamentos Herbarios Chinos , Janus Quinasa 2 , Mitocondrias , Proteínas Proto-Oncogénicas c-akt , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Medicamentos Herbarios Chinos/farmacología , Ratones , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inmunología , Femenino , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Miastenia Gravis Autoinmune Experimental/tratamiento farmacológico , Miastenia Gravis Autoinmune Experimental/inmunología , Proteínas Ligasas SKP Cullina F-box/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Musculares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo

RESUMEN

Myasthenia gravis (MG) is a chronic autoimmune disease mediated by autoreactive T- and B-cells and manifested by progressive pathological muscle weakness and fatigue. Traditional immunomodulatory treatment does not always lead to the clinical picture significant improvement, despite adequate dosage and duration of use. Refractory myasthenia gravis requires new therapeutic approaches development and implementation. The range of target innovative agents in refractory MG includes monoclonal antibodies, which act directly on individual components of the complement system. Based on the results of randomized controlled trials, data on the effectiveness and safety of eculizumab, which inhibits the C5 component of the complement system, is presented. We present our own clinical experience of using eculizumab in a young woman with refractory generalized AChR-positive MG with a rapid decrease in the severity of symptoms to a minimum level and restoration of ability to work, and the absence of adverse events during therapy.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Miastenia Gravis , Humanos , Miastenia Gravis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Adulto , Resultado del Tratamiento , Inactivadores del Complemento/uso terapéutico

RESUMEN

OBJECTIVE: To compare the differential impact of recombinant protein A immunoadsorption (PAIA) or therapeutic plasma exchange (TPE) on neurological functional improvement and quality of life in patients afflicted with severe acute neuroimmune diseases, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and anti-NMDA receptor encephalitis (NMDARE). METHODS: The retrospective study included 29 patients with moderate to severe disability (modified Rankin scale, mRS≥3) due to acute neuroimmune diseases at the second Xiangya hospital from January 2021 to January 2023. The clinical efficacy of PAIA and TPE in improving neurological function (ΔmRS≥1) and the difference in favorable functional outcomes (mRS 0-2) at three months were evaluated. The impact of both treatments on patients' health-related quality of life (HRQoL) was assessed using a visual analog scale (EQ-VAS) score ranging from 0 to 100. RESULTS: The findings revealed that the PAIA group exhibited a significantly higher rate of improvement in modified Rankin scale (mRS) scores (ΔmRS≥1) at the three-month follow-up compared to the TPE group (94.4 % vs. 54.5 %, p = 0.018). However, no statistically significant difference was observed between the two treatment modalities in terms of favorable neurological functional outcomes at the three-month mark. Furthermore, the PAIA group demonstrated a significantly higher EQ-VAS score at 14 days post-treatment compared to the TPE group (60.0 vs. 47.7, p = 0.017). CONCLUSION: In the short-term management of severe acute neuroimmune diseases, PAIA may present a greater probability of improving neurological function and facilitating an earlier enhancement of quality of life compared to TPE.

Asunto(s)

Intercambio Plasmático , Calidad de Vida , Humanos , Intercambio Plasmático/métodos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Técnicas de Inmunoadsorción , Recuperación de la Función , Resultado del Tratamiento , Síndrome de Guillain-Barré/terapia , Síndrome de Guillain-Barré/inmunología , Anciano , Miastenia Gravis/terapia , Miastenia Gravis/inmunología , Adulto Joven

RESUMEN

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.

Asunto(s)

Autoanticuerpos , Miastenia Gravis , Miastenia Gravis/inmunología , Miastenia Gravis/terapia , Miastenia Gravis/patología , Humanos , Autoanticuerpos/inmunología , Receptores Colinérgicos/inmunología , Timoma/inmunología , Timoma/patología , Timoma/terapia , Antígenos de Histocompatibilidad Clase I/inmunología , Receptores Fc/inmunología , Proteínas Tirosina Quinasas Receptoras/inmunología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores

RESUMEN

Recent advances in neuroimmunology have shed light on the pathogenic mechanisms underlying rare neuroimmunologic conditions such as myasthenia gravis (MG) and stiff person syndrome (SPS). Despite the rarity of these conditions, their complex manifestations and potential for irreversible disability necessitate effective therapeutic strategies. This chapter reviews the current understanding of the safety and efficacy of hematopoietic stem cell transplantation (HSCT) in MG and SPS. Several case reports and retrospective studies have demonstrated promising outcomes following HSCT in refractory MG and SPS, with significant clinical improvement and even discontinuation of chronic immunomodulatory therapy in some cases. Furthermore, HSCT may offer insights into the underlying pathophysiologic mechanisms of these conditions, particularly the role of cellular immunity. Although more research is needed to fully understand the impact of HSCT on disease pathology and outcomes, current evidence suggests that HSCT could be a valuable therapeutic option for patients with refractory MG and SPS.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Miastenia Gravis , Síndrome de la Persona Rígida , Síndrome de la Persona Rígida/terapia , Humanos , Miastenia Gravis/terapia , Trasplante de Células Madre Hematopoyéticas/métodos

RESUMEN

Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.

Asunto(s)

Inhibidores del Factor Xa , Intercambio Plasmático , Pirazoles , Piridonas , Humanos , Piridonas/administración & dosificación , Pirazoles/administración & dosificación , Pirazoles/farmacocinética , Intercambio Plasmático/métodos , Inhibidores del Factor Xa/administración & dosificación , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/terapia , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Femenino , Persona de Mediana Edad , Semivida , Masculino , Anciano

RESUMEN

Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient's age was 64 [42-76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3-10] days and the median total length of MV was 14 [10-23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.

Asunto(s)

Miastenia Gravis , Respiración Artificial , Desconexión del Ventilador , Humanos , Femenino , Masculino , Miastenia Gravis/terapia , Miastenia Gravis/fisiopatología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Respiración Artificial/métodos , Respiración Artificial/efectos adversos , Pruebas de Función Respiratoria , Factores de Riesgo

RESUMEN

BACKGROUND: Generalized myasthenia gravis (gMG) can be managed with acetylcholinesterase inhibitors (AChEis; e.g., pyridostigmine), corticosteroids, other immunosuppressive drugs (e.g., tacrolimus), and their combinations. Intravenous immunoglobulin (IVIg) or plasmapheresis (PLEX) may be administered if symptoms persist. PLEX and IVIg are also mainstays of treatment for myasthenic crisis. Recently, efgartigimod was approved in Japan for treating adults with gMG (irrespective of the antibody status) who do not have a sufficient response to corticosteroids and nonsteroidal immunosuppressive therapies. Efgartigimod is generally safe and well tolerated. However, since phase III trials of efgartigimod excluded those with myasthenic crisis, the efficacy of efgartigimod in treating myasthenic crisis is still unclear. Moreover, there are no reports that efgartigimod therapy can reduce the dose of corticosteroids needed to achieve a minimal manifestation status. CASE PRESENTATION: We report the case of a 70-yeat-old woman with gMG who developed a myasthenic crisis. After she was diagnosed with gMG, the patient had been treated with oral corticosteroids and tacrolimus for 1 year. However, she refused to continue taking the medication, and two weeks later, she developed ptosis, dysphagia and dyspnea. The patient was intubated and treated with efgartigimod in combination with steroid therapy, and she recovered without PLEX or IVIg. Afterward, when she experienced worsening of fatigue and increased levels of anti-acetylcholine receptor antibodies, efgartigimod therapy was effective. The patient achieved minimal manifestation status even after the reduction of corticosteroids and showed improvements in the Myasthenia Gravis Activities of Daily Living scales after 4 cycles of efgartigimod infusion. CONCLUSIONS: Our case suggests that efgartigimod can be an alternative drug for achieving minimal manifestation status in patients with myasthenic crisis. Considering its strong efficacy and safety, efgartigimod could be expanded to use as bridging therapy in the acute and chronic phases of gMG.

Asunto(s)

Miastenia Gravis , Humanos , Miastenia Gravis/tratamiento farmacológico , Femenino , Anciano , Quimioterapia Combinada , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación

RESUMEN

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined. METHODS: Using microarray analysis, we analyzed the lncRNA levels in MG. By bioinformatics analysis, LINC01566 was found to potentially play an important role in MG. First, qRT‒PCR was performed to verify the LINC1566 expressions in MG patients. Then, fluorescence in situ hybridization was conducted to determine the localization of LINC01566 in CD4 + T cells. Finally, the impact of LINC01566 knockdown or overexpression on CD4 + T-cell function was also analyzed using flow cytometry and CCK-8 assay. A dual-luciferase reporter assay was used to validate the binding of the TF FOSL1 to the LINC01566 promoter. RESULTS: Based on the lncRNA microarray and differential expression analyses, we identified 563 differentially expressed (DE) lncRNAs, 450 DE mRNAs and 19 DE TFs in MG. We then constructed a lncRNA-TF-mRNA network. Through network analysis, we found that LINC01566 may play a crucial role in MG by regulating T-cell-related pathways. Further experiments indicated that LINC01566 is expressed at low levels in MG patients. Functionally, LINC01566 is primarily distributed in the nucleus and can facilitate CD4 + T-cell apoptosis and inhibit cell proliferation. Mechanistically, we hypothesized that LINC01566 may negatively regulate the expressions of DUSP3, CCR2, FADD, SIRPB1, LGALS3 and SIRPB1, which are involved in the T-cell activation pathway, to further influence the cellular proliferation and apoptosis in MG. Moreover, we found that the effect of LINC01566 on CD4 + T cells in MG was mediated by the TF FOSL1, and in vitro experiments indicated that FOSL1 can bind to the promoter region of LINC01566. CONCLUSIONS: In summary, our research revealed the protective roles of LINC01566 in clinical samples and cellular experiments, illustrating the potential roles and mechanism by which FOSL1/LINC01566 negatively regulates CD4 + T-cell activation in MG.

Asunto(s)

Linfocitos T CD4-Positivos , Activación de Linfocitos , Miastenia Gravis , Proteínas Proto-Oncogénicas c-fos , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Miastenia Gravis/metabolismo , Miastenia Gravis/inmunología , Miastenia Gravis/genética , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Adulto

RESUMEN

The aim of this study was to evaluate clinical and serological differences between the ocular myasthenia gravis (oMG) and generalized MG (gMG). This study is a retrospective chart review, in which data was collected from patients fulfilling 2 of 3 diagnostic MG criteria (positive antibodies, evidence of neuromuscular transmission defect on neurophysiological examination, positive effect of pyridostigmine treatment). 350 patients were included and data concerning demographics and MG medical history were collected. Patients with oMG accounted for 15.7 % of the included patients. The two subgroups differed significantly in oMG having a later age at onset, lower AChR antibody-titers, longer doctor-to-diagnosis delay and less intensive MG treatment. Additionally, patients with oMG were faster at reaching a well-controlled disease state. Thymus pathology, number of antibody-positive (95.9 % of gMG and 94.5 % of oMG), sex, number of other autoimmune diseases and delay before drug stability did not differ between oMG and gMG. In conclusion, oMG is presumably a milder form of gMG characterized by lower AChR antibody-titers, a milder phenotype, and a quicker response to a less aggressive treatment. But otherwise, oMG and gMG show very similar characteristics, including the same frequency of positive AChR antibodies, which seems new compared to previous reports.

Asunto(s)

Autoanticuerpos , Miastenia Gravis , Receptores Colinérgicos , Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/sangre , Miastenia Gravis/inmunología , Femenino , Masculino , Receptores Colinérgicos/inmunología , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Autoanticuerpos/sangre , Anciano , Adulto Joven , Edad de Inicio , Adolescente

RESUMEN

Myasthenia gravis (MG) is a multifaceted autoimmune disorder affecting the postsynaptic neuromuscular junction. In this study, we examined CD4+ and CD8+ T lymphocyte levels and ratios within peripheral blood mononuclear cells (PBMCs) in MG patients. Additionally, we assessed lymphocytes for the expression of CD71, which functions as a transferrin receptor mediating the uptake of iron into the cells. Building on recent discussions regarding CD20 depletion treatments in MG, we also scrutinized lymphocytes for CD20 expression. Comparative analyses were conducted among healthy controls, newly diagnosed MG patients, those undergoing pyridostigmine treatment alone, and MG patients receiving combination therapies. In the patients, the ratio of CD3+CD4+ T lymphocytes to CD3+ T lymphocytes was found to be decreased compared to the healthy controls, while the ratio of CD3+CD8+ cells to CD3+CD4+ cells increased. An increase in the percentage of CD71-expressing lymphocytes was observed in MG patients compared to the healthy control group, while CD20+ lymphocytes exhibited no statistical changes. Moreover, heightened serum lipid peroxidation levels were found in MG patients. These results suggest a possible relationship between iron metabolism, levels of CD71-expressing cells, and lipid peroxidation in MG. Conversely, pyridostigmine treatment reduced the levels of CD71-expressing cells and lipid peroxidation, suggesting potential immunomodulatory and antioxidant impacts of pyridostigmine in MG, either directly or indirectly.

Asunto(s)

Antígenos CD , Peroxidación de Lípido , Miastenia Gravis , Bromuro de Piridostigmina , Receptores de Transferrina , Humanos , Miastenia Gravis/sangre , Miastenia Gravis/inmunología , Miastenia Gravis/tratamiento farmacológico , Masculino , Femenino , Antígenos CD/metabolismo , Persona de Mediana Edad , Adulto , Receptores de Transferrina/metabolismo , Bromuro de Piridostigmina/uso terapéutico , Estudios de Cohortes , Anciano , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Hierro/metabolismo

RESUMEN

BACKGROUND: Disturbed sleep and its impact on quality of life (QoL) are underrecognized in myasthenia gravis (MG). AIMS: To evaluate the quality of sleep in MG using standard sleep questionnaires and assess factors that determine sleep. SETTINGS AND DESIGN: Prospective, cross-sectional, hospital-based study. PATIENTS AND METHODS: Fifty patients on stable drug therapy for at least 1 month and age- and gender-matched controls were assessed using standard sleep questionnaires [Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and NIMHANS Comprehensive Sleep Disorders Questionnaire (NCSDQ)]. RESULTS: Myasthenia Gravis Foundation of America (MGFA) grade was I, IIA, IIB, IIIA, IIIB, and IVA in 11, 19, 3, 10, 6, and 1 respectively. The mean PSQI and ESS scores were similar in patients and controls. Patients with abnormal ESS (>10) were older and had greater neck circumference (P = 0.018 and <0.001). Body mass index was greater in patients with PSQI > 5 (P < 0.05). Age, gender, and clinical severity did not affect PSQI. Compared with ESS and PSQI, NCSDQ showed higher frequency of disturbed sleep, snoring, early morning headache, difficulty in initiation, and maintenance of sleep in MG, although the differences between patients and controls were not significant. No correlation was found between QoL and ESS or PSQI. CONCLUSION: Patients of MG with stable clinical course with adequate treatment have sleep quality comparable with healthy controls. Longitudinal assessment of sleep quality at multiple time points throughout the disease course and correlating with cross-sectional disease severity may further delineate the impact of disease on sleep and QoL.

Asunto(s)

Miastenia Gravis , Calidad de Vida , Trastornos del Sueño-Vigilia , Humanos , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto , Trastornos del Sueño-Vigilia/etiología , Estudios Prospectivos , Calidad del Sueño , Sueño/fisiología , Anciano

RESUMEN

A rare subtype of autoimmune encephalitis consists of antibodies targetting the alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptor in the central nervous system. We describe the clinical presentation and autoimmune profile of the first case of alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis with concurrent anti-acetylcholine receptor antibodies in Pakistan. The patient was a 58-year-old male who presented with the characteristic symptoms of limbic encephalitis with memory loss, irritability, agitation, and confusion. Antibodies against the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptor were detected in both serum and cerebrospinal fluid by indirect immunofluorescence. Computerised tomography of the chest showed an anterior mediastinal mass. The patient was treated with high dose Methylprednisolone and five sessions of plasma exchange. There was a short period of improvement; however, the patient now continues to exhibit irritability, aphasia, confusion, and memory loss. Video-assisted thoracoscopic surgery for mediastinal mass resection and histological testing was planned, however after review by the interventional radiologist the associated risks were deemed too high to proceed with the procedure and biopsy was not done.

Asunto(s)

Miastenia Gravis , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/diagnóstico , Miastenia Gravis/complicaciones , Receptores AMPA/inmunología , Autoanticuerpos/sangre , Encefalitis/inmunología , Encefalitis/diagnóstico , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Encefalitis Límbica/inmunología

RESUMEN

INTRODUCTION/AIMS: The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG). METHODS: A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation. RESULTS: Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use. DISCUSSION: Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.

Asunto(s)

Inhibidores de Hidroximetilglutaril-CoA Reductasas , Miastenia Gravis , Humanos , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Progresión de la Enfermedad , Sistema de Registros , Anciano de 80 o más Años , Adulto , Japón/epidemiología , Estudios de Cohortes , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico

RESUMEN

Myasthenia Gravis (MG) is a rare neurological disease. Although there are intensive efforts, the underlying mechanism of MG still has not been fully elucidated, and early diagnosis is still a question mark. Diagnostic paraclinical tests are also time-consuming, burden patients financially, and sometimes all test results can be negative. Therefore, rapid, cost-effective novel methods are essential for the early accurate diagnosis of MG. Here, we aimed to determine MG-induced spectral biomarkers from blood serum using infrared spectroscopy. Furthermore, infrared spectroscopy coupled with multivariate analysis methods e.g., principal component analysis (PCA), support vector machine (SVM), discriminant analysis and Neural Network Classifier were used for rapid MG diagnosis. The detailed spectral characterization studies revealed significant increases in lipid peroxidation; saturated lipid, protein, and DNA concentrations; protein phosphorylation; PO2-asym + sym /protein and PO2-sym/lipid ratios; as well as structural changes in protein with a significant decrease in lipid dynamics. All these spectral parameters can be used as biomarkers for MG diagnosis and also in MG therapy. Furthermore, MG was diagnosed with 100% accuracy, sensitivity and specificity values by infrared spectroscopy coupled with multivariate analysis methods. In conclusion, FTIR spectroscopy coupled with machine learning technology is advancing towards clinical translation as a rapid, low-cost, sensitive novel approach for MG diagnosis.

Asunto(s)

Biomarcadores , Aprendizaje Automático , Miastenia Gravis , Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/sangre , Femenino , Masculino , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Máquina de Vectores de Soporte , Análisis de Componente Principal , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Anciano , Espectrofotometría Infrarroja/métodos