Myasthenia Gravis Patients Research Articles

Agonist antibody to MuSK protects mice from MuSK myasthenia gravis

Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). MuSK, a master regulator of NMJ development, associates with the low-density lipoprotein-related receptor 4 (Lrp4) to form the signaling receptor for neuronal Agrin, a nerve-derived synaptic organizer. Pathogenic antibodies to MuSK interfere with binding between MuSK and Lrp4, inhibiting the differentiation and maintenance of the NMJ. MuSK MG can be debilitating and refractory to treatments that are effective for AChR MG. We show here that recombinant antibodies, derived from MuSK MG patients, cause severe neuromuscular disease in mice. The disease can be prevented by a MuSK agonist antibody, presented either prophylactically or after disease onset. These findings suggest a therapeutic alternative to generalized immunosuppression for treating MuSK MG by selectively and directly targeting the disease mechanism.

Non-Coding RNAs in Myasthenia Gravis: From Immune Regulation to Personalized Medicine.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by altered neuromuscular transmission, which causes weakness and fatigability in the skeletal muscles. The etiology of MG is complex, being associated with multiple genetic and environmental factors. Over recent years, progress has been made in understanding the immunological alterations implicated in the disease, but the exact pathogenesis still needs to be elucidated. A pathogenic interplay between innate immunity and autoimmunity contributes to the intra-thymic MG development. Epigenetic changes are critically involved in both innate and adaptive immune response regulation. They can act as (i) pathological factors besides genetic predisposition and (ii) co-factors contributing to disease phenotypes or patient-specific disease course/outcomes. This article reviews the role of non-coding RNAs (ncRNAs) as epigenetic factors implicated in MG. Particular attention is dedicated to microRNAs (miRNAs), whose expression is altered in MG patients' thymuses and circulating blood. The long ncRNA (lncRNA) contribution to MG, although not fully characterized yet, is also discussed. By summarizing the most recent and fast-growing findings on ncRNAs in MG, we highlight the therapeutic potential of these molecules for achieving immune regulation and their value as biomarkers for the development of personalized medicine approaches to improve disease care.

Low-intensity aerobic cycle ergometer effects on lung function of myasthenia gravis patients: A randomized controlled trial

Patients with generalized myasthenia gravis (MG) often show restrictive spirometry results. Although regular exercise and physical fitness are linked to better respiratory function, there is limited research assessing the effects of aerobic exercise on lung function in MG patients. The aim of this study was to analyze the effect of low-intensity aerobic exercise using a cycle ergometer on lung function parameters in MG patients. A randomized controlled trial with pre- and post-test was conducted at the Medical Rehabilitation Outpatient Clinic of Dr. Soetomo General Academic Hospital in Surabaya, Indonesia, in 2023. MG patients classified as I−IIb based on the Myasthenia Gravis Foundation of America (MGFA) classification were recruited and randomly divided into treatment and control groups. The treatment group was given low-intensity aerobic exercise using a cycle ergometer, education on lifestyle changes, and breathing exercises (deep and pursed lip breathing). Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory volume ratio (FEVR), were then measured. Measurements were conducted before and after eight weeks of low-intensity aerobic cycle ergometer exercise and compared with those of a control group. A total of 17 MG patients were included in this study. The results showed a significant increase in FVC in the treatment group (p=0.003), whereas no significant change in the control group (p=0.068). A significant increase in FEV1 was observed both in the treatment (p=0.029) and the control group (p=0.016). There was no improvement in FEVR in either group. After the intervention, significant differences were observed in FVC (p=0.009) and FEV1 (p=0.029) between the treatment and control groups. There was no significant difference in FEVR values after the intervention between both groups (p=0.491). In conclusion, eight weeks of low-intensity aerobic cycle ergometer exercise led to significant improvements in FVC and FEV1 among MG patients.

Elevated serum levels of C-terminal agrin fragment in acetylcholine receptor antibody-positive myasthenia gravis

Agrin is essential for neuromuscular junction (NMJ) formation and maintenance. The C-terminal agrin fragment (CAF), generated by neurotrypsin-mediated cleavage of agrin, has been gaining attention as a potential biomarker for sarcopenia. We investigated serum CAF levels in myasthenia gravis (MG), a NMJ disorder. Compared to healthy controls, serum CAF levels were significantly elevated in acetylcholine receptor antibody-positive MG (AChR-MG) patients, but not in muscle-specific kinase antibody-positive MG patients. In AChR-MG, baseline and post-treatment CAF levels inversely correlated with post-treatment MG activities of daily living scores, suggesting that elevated CAF levels may reflect protective mechanisms against AChR-MG pathogenesis, such as improved NMJ regeneration.

Long-Term Bone Density Changes and Fracture Risk in Myasthenia Gravis: Implications for FRAX® Tool Application.

Myasthenia gravis (MG) patients often require long-term glucocorticoid therapy, which may affect bone health. This study aimed to assess long-term changes in bone mineral density (BMD), evaluate osteoporotic fracture incidence, and examine the relationship between MG-specific factors and bone health outcomes over a 10-year period. This single-center, prospective cohort study included 28 MG patients. BMD, T-scores, Z-scores, and bone turnover markers were measured at baseline. FRAX® scores were calculated and adjusted for glucocorticoid dose. Fracture occurrence was monitored for over 10 years. Five (17.9%) patients experienced major osteoporotic fractures during follow-up. The fracture group had significantly lower baseline BMD and T-scores than the no-fracture group. Baseline FRAX® scores for major osteoporotic fracture risk were significantly higher in the fracture group (median 19.0% vs. 5.7%, p = 0.001). The fracture group progressed from osteopenia at baseline to osteoporosis by the end of this study. This study highlights the importance of early and regular bone health assessments in MG patients, particularly those receiving long-term glucocorticoid therapy. The FRAX® tool may be valuable for fracture risk stratification in this population. These findings can inform clinical practice and improve long-term management strategies for MG patients who are at risk of osteoporotic fractures.

Elevated C1s/C1-INH in serum and plasma of myasthenia gravis patients

Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder where acetylcholine receptor (AChR) antibodies induce membrane attack complex formation at the muscle membrane. The C1-inhibitor (C1-INH) regulates the classical pathway and is a promising marker in other autoimmune disorders. Treatment options for AChR antibody MG include complement inhibitors; nevertheless, the early pathway activation in MG remains unclear. Serum and plasma C1s-C1-INH levels were higher in MG patients than in matched healthy controls, supporting early classical pathway activation in most MG patients. These findings allow prospective validation studies of activated C1s as a putative treatment target and potential accompanying biomarker in MG.

Descriptive analysis of therapeutic outcomes between thoracoscopic and transsternal thymectomy in myasthenia gravis patients from 2011 to 2021

BackgroundMyasthenia 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.MethodsThe 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.ResultsThe 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.ConclusionOverall, 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.

Intestinal pseudo-obstruction in a myasthenia gravis patient after thymectomy: A case report and literature review

Intestinal pseudo-obstruction in patients with myasthenia gravis is a rare and poorly understood phenomenon. We report a case coexisting with intestinal pseudo-obstruction and myasthenia gravis. The patient was diagnosed to have myasthenia gravis and underwent thymectomy seven years ago. He was tested positive for anti-acetylcholine receptor antibody and was free of thymoma recurrence during the current illness. Despite being given gastrointestinal decompression and parenteral nutrition, the patient’s gastrointestinal symptoms did not improve. Symptoms were rectified effectively by immunomodulatory therapy. This case adds intestinal pseudo-obstruction to the phenotypic profile of post-thymectomy myasthenia gravis. High titer of AChR antibody might play a role in the pathogenesis of myasthenia gravis with intestinal pseudo-obstruction.

Pitfalls in the Evaluation of Respiratory Failure in Myasthenia Gravis Patients: A Case Series

Objectives To highlight the importance of recognizing different presentations of respiratory failure due to myasthenic and non-myasthenic etiologies in myasthenia gravis (MG) patients. Methods We describe 3 patients with different presentations of respiratory failure in MG. Cases Patient 1 is a 49-year-old female with longstanding MG who presented with lethargy and neck weakness without notable respiratory distress. She was found to be in hypercarbic respiratory failure, which improved with plasmapheresis treatment. Patient 2 is a 58-year-old female who presented with ptosis, dysphagia, and dyspnea requiring intubation. Her hypophonia and dyspnea persisted despite escalation in MG treatment, and further workup revealed glottal stenosis secondary to granulomatosis with polyangiitis. Patient 3 is an 85-year-old female with MG presenting with refractory hypoxia, which was secondary to a large patent foramen ovale resulting in right-to-left shunting. Discussion All 3 cases emphasize the role of clinical reasoning and careful analysis based on thorough history taking, detailed neurologic exam and comprehensive laboratory findings to determine the etiologies for respiratory dysfunction in MG and provide appropriate treatment. Conclusion A lack of overt signs of respiratory distress in MG does not rule out the presence of respiratory failure due to the sedating effect of hypercapnia. There is a need to consider alternative etiologies of hypoxia in MG patients if typical symptoms or signs of MG exacerbations are absent.

A patient treated with ofatumumab for myasthenia gravis in conjunction with systemic lupus erythematosus and thyroid carcinoma.

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. Anti-CD20 monoclonal antibodies, such as ofatumumab demonstrated promising disease control in MG patients. We presented the rare case of a 34-year-old female with acetylcholine receptor-positive myasthenia gravis (AChR-MG), concomitant with systemic lupus erythematosus (SLE) and metastatic thyroid carcinoma, who was treated with ofatumumab and exhibited improvements during follow-up.

Circ_0076490 silencing inhibits MAPK1 expression to decrease the proliferation and increase apoptosis of Jurkat cells by regulating miR-144-3p in myasthenia gravis

ABSTRACT Background Myasthenia gravis (MG) is a both neuromuscular junction and antibody-mediated autoimmune disease, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the role of circ_0076490 in MG and the underlying mechanism remain unknown. Methods RNA levels of circ_0076490, microRNA-144-3p (miR-144-3p), and mitogen-activated protein kinase 1 (MAPK1) were detected by quantitative real-time polymerase chain reaction. Cell viability and proliferation were investigated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine assays, respectively. Cell cycle and apoptosis were assessed by flow cytometry analysis. The putative binding relationship of miR-144-3p and circ_0076490 or MAPK1 was predicted by circular RNA interactome and TargetScan online databases, respectively, and identified through dual-luciferase reporter assay and RNA pull-down assay. Results We observed dramatic increases of circ_0076490 and MAPK1 expression and a decrease of miR-144-3p expression in the peripheral blood of MG patients in comparison with healthy controls. Reduced expression of circ_0076490 induced an inhibitory effect on the proliferation of Jurkat cells and a promoting effect on cell apoptosis. Additionally, miR-144-3p was identified as a target miRNA of circ_0076490, and its depletion attenuated circ_0076490 knockdown-mediated effects on the proliferation and apoptosis of Jurkat cells. MAPK1 was a target gene of miR-144-3p and its overexpression rescued decreased cell proliferation and increased cell apoptosis induced by miR-144-3p introduction. Furthermore, circ_0076490 regulated MAPK1 expression by interacting with miR-144-3p. Conclusion Circ_0076490 knockdown inhibited proliferation and induced apoptosis of Jurkat cells through the regulation of the miR-144-3p/MAPK1 axis, providing potential targets for developing improved therapy of MG.

Clinical characteristics and therapeutic effect of myasthenia gravis coexisting with thyroid eye disease.

Here, we describe the clinical characteristics and therapeutic effects of myasthenia gravis (MG) coexisting with thyroid eye disease (TED). We collated clinical data from MG patients in our hospital between 2012 and 2022 and analyzed the clinical characteristics of MG patients with hyperthyroidism, MG patients with TED and ocular myasthenia gravis (OMG) patients with TED. We recruited 62 MG patients with hyperthyroidism, including 13 MG patients with TED and 10 OMG patients with TED. There were 70 MG patients without hyperthyroidism; 29 of these were OMG. Compared with patients without hyperthyroidism, patients with hyperthyroidism had an earlier age at onset and milder clinical symptoms (P < 0.05). The incidence of thymus hyperplasia in patients with hyperthyroidism and TED was significantly lower than that in patients without TED (38.5% vs. 69.4%, P < 0.05); these patients also had a significantly lower antibody titer for the acetylcholine receptor [0.72 (0.27, 14.93) nmol/L vs. 2.38 (0.28, 49.51) nmol/L, P < 0.05]. Diplopia was significantly more frequent in OMG patients with TED than in patients with OMG (84.6% vs. 44.8%, P < 0.05), and the rate of diplopia in OMG patients with TED was significantly higher after treatment with bromostigmine and glucocorticoid (69.2% vs. 3.4%, P < 0.05). MG patients with TED had a significantly lower incidence of thymus hyperplasia and a lower antibody titer for the acetylcholine receptor. Patients with OMG and TED are more likely to develop diplopia; it is very difficult to treat diplopia in these patients.

The Injected Plasma of Myasthenia Gravis Patient with A Low T-reg Level Caused Clinical Myasthenic Syndromes in Swiss-Webster Mice

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease affecting neuromuscular junction involvement. The finding that T-reg level in MG patients was lower than that in normal persons leads to the idea that the primary pathology of the disease is T-reg dependent. The T-reg level of MG patients seems to be decreasing compared to that of normal persons. The study was conducted to observe the contribution of T-reg level in plasma injected into Swiss-Webster mice to develop clinically and pathologically myasthenic syndromes.METHODS: Swiss-Webster mice were grouped into three groups: the groups received plasma with normal, low, and high T-reg levels, respectively. The T-reg levels of the mice were measured with flow cytometry analysis and a human regulatory T-cell cocktail for T-cell surface cell marker. The motor function, interleukin (IL)-2, interferon (IFN)-γ, and thymus weight of mice were measured after the injection. Histopathological examination was performed to analyze mice’s muscles and thymus.RESULTS: The result identified that the motor function (2-week treatment group: p=0.021 and 3-week treatment group: p=0.032) and muscle width (p=0.014, p=0.032 and p≤0.001) were significantly lower in the low T-reg level plasma group compared to control and high T-reg level plasma groups. The thymus showed an increase in weight without an increase in the cortex-medulla ratio of the thymus, indicating hyperplasia. Both IL-2 and IFN-γ levels were lower in the low and high T-reg level groups compared with the control group, indicating the autoimmune process.CONCLUSION: Low T-reg level was associated with lower motor function, muscle width, increased thymus weight, as well as lower IL-2 and IFN-γ levels. T-reg level contributed to clinical myasthenic syndromes but not pathological findings. This research method is expected to be a basis for the development of animal models with Swiss-Webster mice.KEYWORDS: animal model, Myasthenia gravis, Swiss-Webster mice

Targeted Treatments for Myasthenia Gravis in Children and Adolescents.

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis.

Effect of Follicular T Helper and T Helper 17 Cells-Related Molecules on Disease Severity in Patients with Myasthenia Gravis.

Contribution of T helper 1 and 2 cells-related cytokines to pathogenesis of myasthenia gravis (MG) is well known. Recently, the contribution of follicular T helper (Tfh) and T helper 17 cells-related molecules to the pathogenesis has gained importance. In this study, we aimed to evaluate the changes in Tfh- and Th17-related molecules before and after rescue therapy in patients with myasthenic crisis (cMG) and to reveal the molecular differences between stable MG and cMG patients. Patients with stable generalized MG (gMG) and cMG were classified according to Myasthenia Gravis Foundation of America (MGFA) classification. Serum samples were collected from cMG patients both before and after rescue therapy (plasmapheresis or intravenous immunoglobulin [IVIg]). Serum levels of Tfh- and selected Th17-related molecules (IL-22, IL-17A, CXCL13, sPD-L1, sICOSLG, and sCD40L) were analyzed by commercial ELISA kits. Twelve cMG (6 for IVIg, 6 for plasmapheresis) and 10 gMG patients were included in the study. A decrease in serum sPD-L1 and CXCL13 levels was observed in cMG patients after treatment, regardless of the treatment modality (p &lt; 0.05). In contrast, serum sICOSLG levels decreased only in patients treated with IVIg (p &lt; 0.05) and serum IL-22 levels increased in patients receiving plasmapheresis (p &lt; 0.05). cMG patients had higher serum IL-17A levels compared to stable patients (p &lt; 0.001) and its level was positively correlated with disease severity (r = 0.678, p = 0.001). Our results confirm the contribution of Tfh- and Th17-related cell pathways to MG pathogenesis. Both IVIg and plasmapheresis appear to be effective in reducing Tfh- and Th17-related cytokine/molecule levels in cMG patients. Increased serum IL-17A levels may contribute to disease severity.

Conventional dendritic cells are more activated in the hyperplastic Thymus of myasthenia gravis patients

IntroductionDendritic cells (DCs) are crucial to form ectopic germinal centers (GCs) in the hyperplastic thymus (HT), which are typically found in anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG) patients. However, the characteristics of such DCs in the HT and their roles in thymic hyperplasia formation remain unclear. MethodsWe collected thymic tissue from MG patients and patients who underwent cardiac surgery. The tissues were cut into sections for immunohistochemistry and immunofluorescence or digested into a single cell suspension for flow cytometry. ResultsIn addition to formation of ectopic GCs, we found that the proportion of the medulla in the thymic parenchyma was higher than that in the cortex (areacortex/areamedulla, 1.279 vs. 0.6576) in the HT of MG patients. The density of conventional dendritic cells (cDCs) in the HT was 131 ± 64.36 per mm2, whereas in normal thymic tissue, the density was 59.17 ± 22.54 per mm2. The more abundant cDCs expressed co-stimulatory molecules (CD80 and CD86) strongly. Moreover, the more abundant subset was mainly CD141+ DCs (cDC1s), accounting for an increase from 15% to 29%. However, these increased cDC1s appeared to be unrelated to Hassall's corpuscles and ectopic GCs. ConclusionThymic hyperplasia in MG patients is manifested as an increase in the proportion of the thymic medulla accompanied by increases in the density and functional activation as well as changes in the subset composition of cDCs.

Serological indication of chronic inflammatory demyelinating polyneuropathy as an extrahepatic manifestation of hepatitis E virus infection

Guillain–Barré syndrome and neuralgic amyotrophy have been associated with hepatitis E virus (HEV) genotype 3 infections, while myasthenia gravis (MG) has been associated with HEV genotype 4 infections. However, whether chronic inflammatory demyelinating polyneuropathy (CIDP) is associated with HEV infections has not been conclusively clarified yet. 102 CIDP patients, 102 age- and sex-matched blood donors, 61 peripheral neuropathy patients (non-CIDP patients), and 26 MG patients were tested for HEV and anti-HEV IgM and IgG. Sixty-five of the 102 (64%) CIDP patients tested positive for anti-HEV IgG and one (1%) for anti-HEV IgM. No other patient tested positive for ati-HEV IgM. In the subgroup of CIDP patients with initial diagnosis (without previous IVIG treatment), 30/54 (56%) tested positive for anti-HEV IgG. Anti-HEV rates were significantly lower in blood donors (28%), non-CIDP peripheral neuropathy patients (20%), and MG patients (12%). No subject tested positive for HEV viremia. CSF tested negative for in 61 CIDP patients (54 patients with primary diagnosis). The development of CIDP but not non-CIDP polyneuropathy may be triggered by HEV exposure in an HEV genotype 3 endemic region. The increased anti-HEV seroprevalence in CIDP patients is not a consequence of IVIG therapy.

Efgartigimod as a fast-acting add-on therapy in manifest and impending myasthenic crisis: A single-center case series

Efgartigimod was the first-in-class neonatal Fc receptor antagonist approved for the treatment of acetylcholine receptor antibody positive (AChR+), Myasthenia Gravis Foundation of America (MGFA) Class II-IV generalized myasthenia gravis (gMG) patients. As a novel therapy, the clinical experiences are still lacking, especially for the use of efgartigimod in manifest and impending myasthenic crisis (IMC). We reported three AChR+, gMG patients, two with myasthenic crisis (MC) and one with IMC, treated with efgartigimod. MGFA class, MG-Activity of Daily Living score (MG-ADL), Quantitative MG score (QMG), and Muscle Research Council sum score (MRC), concentration of anti-AChR antibody, IgG, globulin, and albumin, subsets of T and B lymphocyte were evaluated or measured before, during and after efgartigimod treatment. All patients showed fast and robust response to efgartigimod with marked improvement in MGFA, MG-ADL, QMG, and MRC scores. Patient 1 did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. She extubated at 7 days after the first infusion and got rid of NIV after 14-days treatment. Patient 2 and patient 3 directly used efgartigimod when symptoms were not ameliorated by adjusting of oral drugs. Patient 2 wean from BiPAP at seven days after the first infusion. Patient 3 in IMC status, overcame the severe dysphagia at three days after the first infusion. Clinical symptoms continued to improve 1–2 weeks after discharge. Concentration of anti-AChR antibody, IgG and globulin were remarkably reduced by efgartigimod treatment. Our study supported that efgartigimod could act as a fast-acting rescue therapy for patients with MC or IMC. Larger studies from multicenter are required to provide further evidence.

Insights from CD71 presentation and serum lipid peroxidation in myasthenia gravis – A small cohort study

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.

Effectiveness and Safety of Mycophenolate Mophetil in Myasthenia Gravis: A Real-Life Multicenter Experience.

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness due to autoantibodies targeting neuromuscular junction proteins. Mycophenolate mofetil (MMF), an immunosuppressive therapy, has shown potential for managing MG with fewer side effects compared to other treatments. This study aims to evaluate the effectiveness and safety of MMF in MG patients in a real-life multicenter setting. A retrospective cohort study was conducted on generalized MG patients, refractory to azathioprine (AZA) and treated with MMF alone or with steroids, at three Italian centers from January 2011 to February 2024. Patients were assessed using the Myasthenia Gravis Foundation of America (MGFA) classification, MG composite score (MGCS), and MG activity of daily living (MGADL) scores at baseline, 6, 12, 18, and 24 months. Statistical analyses included the Spearman correlation, the Friedman test, and ANOVA. Thirty-two patients were enrolled (13 males, mean age 66.5 ± 11.5 years). Significant improvements in MGADL and MGCS scores were observed at 6 and 12 months (p < 0.001), with continued improvement over 24 months. Side effects were reported in 12% of patients. MMF showed a faster onset of symptom control compared to azathioprine, with a significant improvement noted within 6 months. A recent study found that MMF and AZA were equally effective in improving patients' quality of life, but because AZA had more serious adverse events than MMF, lower doses of AZA were therefore recommended to reduce the adverse events while maintaining efficacy. Conversely, results showed that MMF is effective and well-tolerated in the long-term management of MG, providing faster symptom control and a favorable safety profile. Future prospective studies with larger cohorts are needed to confirm these findings and explore sex differences in response to MMF treatment.