antibodies

2026-06-24 | Telitacicept in refractory juvenile generalized myasthenia gravis: a case report and collective analysis.

Refractory or corticosteroid-dependent juvenile generalized myasthenia gravis (gMG) remains a clinical challenge, given the scarcity of available regimens and prominent corticosteroid-related adverse effects. Telitacicept, a dual inhibitor of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), has demonstrated efficacy in adult gMG, whereas clinical data in pediatric patients remains limited. To evaluate the clinical response, tolerability, and potential corticosteroid-sparing benefit of telitacicept in juvenile refractory gMG. We report one new case of juvenile refractory gMG treated with telitacicept and review three previously reported pediatric gMG cases. Collective analysis was performed to evaluate key outcomes, including changes in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis (QMG) score, corticosteroid dose reduction, and adverse events. In the index case, telitacicept reduced the MG-ADL score from 3 to 0 and the QMG score from 10 to 3 by week 12. By week 32, the MG-ADL score remained at 0, while the QMG score further decreased to 2, accompanied by a 41.6% reduction in corticosteroid dose. The patient developed mild injection-site erythema and pruritus on only one occasion, which resolved spontaneously. She also had a mild upper respiratory tract infection that resolved within one week following symptomatic treatment. Collective analysis of the four included patients (age range: 7-17 years) showed that three cases (Cases 1, 2, and 4) achieved marked improvement (≥3-point reduction in the MG-ADL score) at 3 months. By 5-6 months, all patients presented sustained clinical improvement with a ≥2-point reduction in the MG-ADL score. No severe adverse events were reported. Telitacicept may be of clinical value and well-tolerated, and may exert a corticosteroid-sparing benefit in juvenile refractory gMG, providing preliminary real-world clinical observations for this understudied population. Further large-scale prospective studies are warranted to confirm these findings.

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2026-06-09 | Results from the ADAPT JR Study Investigating Intravenous Efgartigimod in Juvenile Generalized Myasthenia Gravis (S19.002)

To present interim results of ADAPT JR (NCT04833894), a Phase 2/3 trial assessing pharmacokinetics, pharmacodynamics, safety, and activity of intravenous (IV) efgartigimod in participants with acetylcholine receptor antibody–positive (AChR-Ab+) juvenile generalized myasthenia gravis (gMG) to confirm an age-appropriate dose in this population.

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2026-04-29 | Rituximab in the treatment of myasthenia gravis: a review of current evidence

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction caused by pathogenic autoantibodies targeting acetylcholine receptors (AChR), muscle-specifi c tyrosine kinase (MuSK), or other postsynaptic membrane components, characterized by pathological muscle fatigue and weakness. Rituximab, a monoclonal antibody targeting CD20 that induces B-cell depletion, demonstrates diff erential effi cacy depending on the serological subtype of the disease. In MuSK myasthenia gravis, rituximab induces a robust and sustained therapeutic response by depleting precursor cells of short-lived plasmablasts that produce pathogenic IgG4 antibodies. In AChR-positive myasthenia gravis, rituximab effi cacy is more variable and responses are often delayed, as a substantial proportion of pathogenic antibodies are produced by long-lived CD20-negative bone marrow plasma cells capable of sustaining antibody production independently of precursor B cells. Nevertheless, early rituximab administration in patients with recent disease generalization may accelerate achievement of Minimal Manifestation Status (MMS) and reduce the need for rescue therapy. In pediatric practice, rituximab represents a valuable therapeutic option for severe and refractory juvenile myasthenia gravis. In this review, we synthesize data from randomized and observational studies, discuss dosing regimens, safety profi le, and the role of rituximab in current treatment algorithms.

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2026-04-14 | Clinical Characteristics of Childhood-Onset Myasthenia Gravis in a Large Chinese Cohort.

Among the new cases of myasthenia gravis in China, the proportion of new childhood-onset myasthenia gravis (CMG) patients ranges from 10.3% to 12.6% and is increasing annually. Nevertheless, it remains a rare disease with limited extensive cohort studies. This study aimed to summarize and describe the clinical characteristics of CMG patients in China. We reviewed the data from CMG patients treated at the Center for Myasthenia Gravis in Hebei Province between 2013 and 2023 and finally included data from 1031 patients. The gender ratio (male: female) was 1:1.4 and the median age of onset was 5 years, with a single peak at ages 1-3 years. Within the cohort, family history accounted for 1.7% (18/1031) of the patients. Furthermore, common cold was the most prevalent medical history factor in the cohort, accounting for 4.8% of the total patients. Overall, 62.4% (643/1031) and 0.5% (5/1031) of patients tested positive for acetylcholine receptor antibodies (AChR-Abs) and muscle-specific kinase antibodies (MuSK-Abs), respectively. In addition, the AChR-/MuSK-Ab-double positive rate was 0.1% (1/1031), whereas that for MuSK/AChR-Ab double negativity was 37.25% (384/1031). The Myasthenia Gravis Foundation of America (MGFA) I classification grade was high across all age groups, with the remaining classification grades increasing with age. In addition, ocular weakness as an initial symptom was high across all age groups, and as the age of the patients increased, the proportion of patients with weakness in the limbs, bulbar, and respiratory also increased. Finally, the AChR-Ab titer level was lowest in patients with MGFA I classification and may be related to prognosis. CMG has a peak incidence at ages 1-3 years, with some familial predisposition and a predominance of high MGFA I classification and AChR-Ab positivity. The complexity of the initial symptoms in CMG patients is related to increasing age. Interestingly, the AChR-Ab titer levels may be a potential factor in predicting patient prognosis.

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2026-03-29 | FEATURES OF CHILDHOOD MYASTHENIA GRAVIS

Sri-udomkajorn S. et al. Childhood myasthenia gravis: clinical features and outcomes. J Med Assoc Thai. 2011. Z-X Yang, Xu K-L, Xiong H. Clinical characteristics and therapeutic evaluation of childhood myasthenia gravis. Exp Ther Med. 2015. Elsakka E.E., Elmekky M.H., Omar T.E. Childhood myasthenia gravis: clinical characteristics, treatment strategies, and outcome. Alexandria J Pediatr. 2021. Bi Z. et al. Clinical features and prognostic factors of childhood-onset myasthenia gravis in a large Chinese cohort. Pediatr Neurol. 2023. Mirzaeva O., Khozhimatova M.Sh. Childhood myasthenia: clinical and instrumental characteristics, modern approaches to diagnosis and treatment.

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small molecules

2026-07-30 | Cytokine Changes With Effective Drug Therapy for Juvenile Myasthenia Gravis.

In order to investigate the therapeutic mechanism of Jianpiyiqi Granule in juvenile myasthenia gravis (JMG) and find the immune-associated cytokines or signaling pathways targeted by this intervention. (1) We extracted JMG serum samples from the sample bank of the Hebei Provincial Key Laboratory of Myasthenia Gravis before and after treatment. (2) Using Olink Immune Response Panel detects serum cytokines. Data were collated and analyzed using statistical software. Differentially expressed proteins (DEPs) were visualized using heat maps, volcano plots, and other tools. Differentially expressed cytokines were analyzed using KEGG enrichment pathway analysis to identify the relevant signaling pathways they participate in. (1) Twelve of 92 cytokines were found to be differentially expressed from 20 patients before and after treatment, namely AXIN1, CCL11, CCL13, CCL20, CCL25, CCL3, CD40, IL12B, S100A12, SIRT2, SLAMF1, and STAMBP (|log2FC| > 0.263; false discovery rate (FDR)-adjusted p < 0.05). IL12B was upregulated while AXIN1, CCL11, CCL13, CCL20, CCL25, CCL3, CD40, S100A12, SIRT2, SLAMF1 and STAMBP were downregulated after treatment. Notably, three of these-CCL11, IL12B, and STAMBP-showed stronger statistical evidence, with FDR-adjusted p < 0.01 and |log2FC| > 0.263. (2) The following pathways were obtained by KEGG enrichment analysis of 12 cytokines: cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, Toll-like receptor (TLR) signaling pathway, intestinal immune network for IgA production, IL-17 signaling pathway, NF-kappa B signaling pathway. (3) CCL11 and CCL20 were enriched in the IL-17 signaling pathway. We used enzyme-linked immunosorbent assay (ELISA) to retest additional serum samples before and after treatment from 12 JMG patients before and after treatment. The results showed a significant decrease in CCL11 and CCL20 in after-treatment serum (p < 0.05). Drug therapy for JMG revealed 12 differentially expressed cytokines. Due to the exploratory nature and sample volume constraints, only two candidate cytokines were validated by ELISA. We found that the cytokines CCL11 and CCL20-associated with the IL-17 signaling pathway-were downregulated after treatment. The drug therapy may inhibit MG progression by reducing the expression of IL-17-associated cytokines. At the same time, the drug reduced the expression of CCL3, CCL13, CCL25, and CD40, which may play a role in the abnormal proliferation of thymocytes and chronic inflammatory response at the neuromuscular junction. Future studies with multiplex assays are needed to confirm the involvement of other differentially expressed cytokines, such as SIRT2 and AXIN1, which may contribute to disease mechanisms outside the identified pathways.

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2026-05-01 | D27-12 Recurrent Respiratory Failure in a Child With OSA: Uncovering Myasthenia Gravis

Abstract Introduction Juvenile myasthenia gravis (MG) is a rare form of the disease that can present in children. Most children, especially those under the age of 11, initially present with ocular symptoms such as ptosis and diplopia, while respiratory involvement typically emerges later in more severe disease. We present a case of a child with severe obstructive sleep apnea (OSA) who presented with recurrent episodes of acute hypercarbic respiratory failure, ultimately leading to the diagnosis of MG. Case A 7-year-old female with history of velopharyngeal insufficiency was followed in pulmonology clinic for asthma, recurrent respiratory infections, and OSA. Despite tonsillectomy, adenoidectomy, and palatoplasty, a repeat polysomnography showed severe OSA (obstructive apnea-hypopnea index of 120/hr), hypoxemia and alveolar hypoventilation. OSA was optimally managed with nocturnal bilevel positive airway pressure (BPAP). Over a four-month period, the patient experienced intermittent but progressive fatigue and increased work of breathing with poor weight gain. This was complicated by recurrent admissions for acute hypercarbic respiratory failure in the absence of identifiable triggers, with negative infectious work up and requiring escalation of respiratory support. Her symptoms and findings on exam, including truncal weakness, raised concern for hypoventilation in the setting of neuromuscular weakness. Spirometry demonstrated significant symmetric reduction in FEV1 and FVC, suggestive of a restrictive defect. Maximum inspiratory pressure (MIP) was severely reduced at 13cmH2O (25% predicted). During a hospitalization, the patient underwent extensive evaluation by neurology and genetics, ultimately leading to a diagnosis of muscle- specific tyrosine kinase (MuSK) myasthenia gravis. Initiation of treatment with pyridostigmine and prednisone led to notable improvements in her sleep symptoms, muscle strength, and weight gain. One month follow-up after diagnosis, she had improvement in MIP to 22cmH2O (42% predicted), and in FEV1 and FVC (Figure 1). Discussion This case highlights the complexity of diagnosing MG in children. The incidence of MG in pediatric populations is estimated to be approximately 1.5 cases per million children per year, and the diagnosis is complicated by the range of symptoms at presentation and a wider differential diagnosis. The initial symptoms often include extraocular muscle weakness and ptosis, with more severe presentations including respiratory symptoms. MuSK MG is a more severe subtype of MG, occurring in &lt; 10% of all cases of MG, and often presenting with earlier, more frequent, respiratory crises. This case shows the importance of considering myasthenia gravis in a pediatric patient with intermittent extreme fatigue, muscle weakness and hypoventilation. This abstract is funded by: None

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2026-04-30 | Myasthenia Gravis- Same Disease Yet Not SimilarA Case Series

Introduction: Myasthenia gravis (MG) and related myasthenic syndromes show striking heterogeneity in phenotype, investigations, and treatment response, often complicating timely diagnosis and individualized management. We describe a series of four patients with myasthenic syndromes evaluated at AIIMS Bhopal, highlighting clinical presentation, key diagnostic work‑up (including antibody testing, neurophysiology, neuroimaging, and next‑generation sequencing when indicated), treatment strategies, and short‑term outcomes. Case Reports: One acetylcholine receptor antibody–positive generalized MG patient developed impending myasthenic crisis precipitated by infection and suboptimal pyridostigmine dosing, improving with optimized anticholinesterase therapy, ventilatory support, intravenous immunoglobulin, and rituximab. A second patient with smoldering childhood onset ocular weakness with family history decoded at sixth decade. A third patient unveils approaching a chronic progressive external ophthalmoplegia (CPEO) phenotype. The fourth, an AChR‑positive MG patient prenting with sudden hemiparesis and how we approached. Conclusion This series underscores that ostensibly similar “myasthenic” presentations can reflect diverse autoimmune, genetic, and structural etiologies, and that meticulous clinical assessment, rational use of electrophysiology and genomics, and context‑sensitive therapeutic tailoring are crucial for optimal outcomes. Keywords: Myasthenia Gravis, Myasthenic crisis, Congenital Myasthenic Syndrome, Glioma.

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2026-03-03 | Efficacy and safety of immunosuppressants and immunomodulators in juvenile myasthenia gravis: a systematic review and meta-analysis.

In the present meta-analysis, we aimed to explore the efficacy and safety of immunosuppressants and immunomodulators for the treatment of juvenile myasthenia gravis (JMG). We conducted a systematic search for studies published between January 1st, 2000 and July 28th, 2025, in PubMed, Embase, Web of Science, and the Cochrane Library. Statistical analyses were performed using Stata (version 16.0). Cochran's Q test and the I2 statistic were used to assess the heterogeneity among the included studies. If significant heterogeneity existed (I2 ≥50% or P < 0.05), the random effects model was used; otherwise, the fixed effects model was used to calculate the pooled results. A total of 3029 articles were retrieved. This meta-analysis included 9 cohort and case-control studies, 11 case series, 3 single-arm studies, and 1 randomized controlled trial, focusing on tacrolimus, glucocorticoids, monoclonal antibodies, and intravenous immunoglobulin. Regarding tacrolimus, 9 studies involving 310 patients assessed the efficacy of tacrolimus for treating JMG. The results showed a significant reduction in both the Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores. Moreover, tacrolimus treatment allowed for a reduction in steroid dosage, with a response rate of 0.862 (95% CI: 0.716-0.967). For monoclonal antibodies, 6 studies with 67 patients analyzed the efficacy for JMG. The response rate of monoclonal antibodies was 0.993 (95% CI: 0.935-1.000). Descriptive analyses were conducted for glucocorticoids and IVIG. Besides, 5 studies with 348 patients assessed the efficacy of glucocorticoids for JMG. Included studies showed that the efficacy rate of glucocorticoid monotherapy for isolated ocular myasthenia gravis (OMG) was higher than that for patients with both OMG and generalized myasthenia gravis (GMG). Finally, regarding the use of IVIG, 4 studies reported efficacy for JMG. These investigations reported a response rate ranging from 47.06% to 94.3% for IVIG therapy. In summary, this was the first comprehensive meta-analysis of immunosuppressants and immunomodulators in JMG. However, most included studies were single-center retrospective observational studies. Future prospective multicenter studies are needed to further investigate the efficacy and safety of immunosuppressants and immunomodulators in JMG.

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2026-02-02 | Corticosteroid-Refractory Juvenile Myasthenia Gravis: Treatment Responses and Prognosis in a Large Chinese Cohort.

Some patients diagnosed with juvenile myasthenia gravis (JMG) have corticosteroid-refractory myasthenia gravis (CRMG). The aim of this study was to evaluate the biomarkers of corticosteroid (CS) responsiveness and refractoriness in children, and the overall prognosis of patients after receiving nonsteroidal immunosuppressants (ISs). This cross-sectional study was conducted at the Department of Pediatrics, Xiangya Hospital, Central South University. Data of the patients diagnosed with JMG from 2010 to 2023 were collected and analyzed. Two hundred and seventy-five patients were included in this study; 215 utilized CS, of whom 44.2% had CRMG. Ptosis only was an independent predictor of CS responsiveness (OR = 2.13, SE = 0.36, OR 95% CI = 1.05-4.32, p value = 0.003). The presence of acetylcholine receptor antibodies (AChR-Abs) was an independent predictor of CS refractoriness (OR = 2.78, SE = 0.48, OR 95% CI = 1.09-7.05, p value = 0.033). At last follow-up, 65.8% of the CRMG patients responded to ISs including tacrolimus, azathioprine, intravenous immunoglobulin, mycophenolate mofetil, and rituximab. About 71.0% of the patients that received ≤ 2 ISs were responders; however, only 14.3% of the patients that received subsequent ISs responded. This study provides an approximate prevalence of CRMG in children, as well as predictors of CS responsiveness and refractoriness, which can guide clinicians in prescribing alternative ISs in a timely manner. It can also help researchers understand the burden of CRMG in children when developing promising new therapies.

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cell therapies

2026-04-06 | Centrifugal Versus Membrane-Based Therapeutic Plasma Exchange in Pediatric Seronegative Neuroimmune Disorders: Neurologic Outcome and Age Specific Safety Profile.

This study evaluated the effectiveness of therapeutic plasma exchange (TPE) modalities in seronegative pediatric neuroimmune disorders, focusing on acute therapy response, 6-month neurological outcomes, and age-stratified adverse events. Retrospective observational cohort between 2018 and 2024. Neurological outcomes were assessed at five predetermined set points during 6 months. Forty-six children underwent 304 TPE procedures in 49 sessions. Early favorable recovery were 84% for autoimmune-encephalitis, 75% for CNS-demyelinating-disorders, 83.3% for Guillan-Barre-syndrome, 66.7% of Juvenile-Myasthenia-Gravis cases. Six-months neurological outcome showed similar recovery rates irrespective-of-TPE-modality used (F[4169] = 0.53, p = 0.711; F[4470] = 0.69, p = 0.602 for CNS and PNS disorders). Adverse events occurred in 20.1% of TPE sessions, were largely age-dependent rather than disease-category or modality-driven, with a 0.891-fold reduction in the likelihood of AE occurrence for each-year increment (OR = 0.891, 95% CI: 0.825-0.962, p = 0.003). Centrifugal and membrane-based TPE are associated with good neurological recovery in seronegative pediatric neuroimmune disorders. Patient age, rather than apheresis modality or disease subtype, has emerged as the primary determinant of the adverse event profile.

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2019-02-07 | Plasmapheresis in Treatment of Myasthenia Gravis

Treatment of myasthenia gravis is still a rather difficult task, since there is no single tactic to use different drugs (corticosteroids, rituximab, immunoglobulins), especially since it is associated with a number of side effects. They are not able to remove the accumulating autoantibodies and immune complexes, the large size of which does not allow them to be excreted by the kidneys as well. Special problems of treatment arise when myasthenic crises develop associated with respiratory failure requiring artificial lungs ventilation. Plasmapheresis can help to solve this for it is possible to remove antibodies and other pathological metabolites. In addition, regular plasmapheresis is able not only to prevent exacerbations but also to reduce doses of the maintenance therapy with less risk of their side effects, which is confirmed by our own experience.

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2017-10-01 | Early fast-acting treatment strategy against generalized myasthenia gravis

Background: Long-term full remission is rare in myasthenia gravis (MG) patients. Minimal manifestations (MM) or better status with prednisolone at ≤5 mg/day (MM-or-better-5mg) was identified as a practical treatment target, as the health-related quality of life of patients with this status is as good as that of complete stable remission. However, the percentage of patients who achieve MM-or-better-5mg is not high, this indicates that changes in treatments are needed to increase treatment success. Therapeutic strategies that aggressively use non-oral fast-acting immunotherapies such as plasmapheresis, intravenous methylprednisolone, and intravenous immunoglobulin from early stages of treatment (early fast-acting treatment strategies, EFT) are reported.

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2015-09-10 | Myasthenia: Novel antigens and therapies

Myasthenia gravis with acetylcholine receptor (AChR) antibodies is the most well-known acquired autoimmune disorder of the neuromuscular junction. MuSK, LRP4, Agrin, ColQ and the VGCC are other antigens at this synapse that are accessible to antibodies. Each is associated with a distinct clinical phenotype. In myasthenic disorders of the postsynaptic muscle membrane ocular or bulbar weakness predominates, while the presynaptic disorder, Lambert–Eaton myasthenic syndrome, presents with proximal leg weakness. The genetic background indicates differences, even between groups of different ages within one autoimmune disorder. HLA-B8DR3 is associated with early-onset AChR MG, but not with late-onset AChR. The immunopathogenesis is also significantly different. AChR MG is caused by complement activating IgG1 antibodies, while MuSK antibodies are IgG4, which cannot activate complement, but mechanically block the MuSK-LRP4 complex. These insights have direct consequences for the choice of therapy. Although several symptomatic or immunosuppressive treatments are available, about 15% of MG patients have been found refractory to immunotherapy or suffers from severe side effects. Symptomatic therapy includes acetylcholinesterase inhibitors. The role of thymectomy in early-onset AChR MG is studied in an ongoing international trial. Plasma exchange or intravenous immunoglobulin treatment are used for treatment of myasthenic crisis, and corticosteroids and several immunosuppressive drugs for chronic immunosuppressive treatment. An increasing number of new drugs are being tested in MG. These drugs often have their origin in transplantation medicine, the treatment of cancer or other autoimmune disorders. To adequately test these new therapies a well defined study population, as well as outcome measures are necessary.

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2014-03-27 | Feasibility of Pediatric Plasma Apheresis in Intensive Care Settings

Therapeutic plasma apheresis or exchange (TPE) in the pediatric population is technically challenging. Moreover, there is generally an apprehension in using TPE in children compared to adults. Recently, usage of TPE has evolved and is now being used in heterogenous clinical conditions. Its usefulness is classified by the American Society for Apheresis (ASFA) into various categories ranging from I to IV. The objective of this paper was to review the procedure in context of clinical indications, complications and outcomes in children. For this purpose, we retrospectively reviewed all TPE procedures performed on inpatients of 3 to 16 years of age during a 6-year period (2007-2012). A total of 130 procedures were performed on 28 patients (M : F ratio of 1:1) with median age (range) of 8.8 (4-16) years. All procedures were done using the continuous cell-separator centrifugal method. Due to organ dysfunctions, the majority of procedures (N = 26 of 28 or 92% patients) were performed in the pediatric intensive care unit. Twenty-three, four and one patient belonged to ASFA categories I, II and III, respectively. The most common indications were neurological disorders (N = 13 or 46.4%), comprised of Guillain-Barré syndrome (N = 10) and myasthenia gravis (N = 3). Hematological disorders (N = 10 or 35.7%) including thrombotic thrombocytopenic purpura-hemolytic uremic syndrome were a close second. Complete recovery was seen in 23 patients (84%). Trivial adverse effects were observed in 18/130 (13.8%) procedures. Major complications including cardiac arrest, hypotension and transfusion-related acute lung injury were observed in 5/130 or 3.8% of procedures. However, there was no procedure-related death though five patients died during treatment due to underlying pathology. In conclusion, TPE is a safe and effective option in sick children for appropriate indications. An experienced staff with sound procedural skills is imperative for successful therapy.

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vaccines

2026-06-30 | Proxy immunization enabling yellow fever vaccination after thymectomy.

Yellow fever (YF) vaccination is generally contraindicated in individuals with thymic disorders because of the risk of YF vaccine-associated viscerotropic disease (YEL‑AVD). As YF transmission expands and global travel increases, protection may still be indicated for selected patients with prior thymectomy. We report a 25‑year‑old woman with childhood thymectomy for acetylcholine receptor antibody-positive generalized myasthenia gravis, now in long‑term remission without immunosuppression, who required YF prevention. Immune competence was evaluated using monitored orthoflaviviral proxy immunization with the live‑attenuated tetravalent dengue vaccine (TAK‑003). She experienced mild reactogenicity and developed dengue‑specific antibodies and T‑cell responses, with preserved B-cell maturation. After confirming orthoflaviviral immune competence, she received YF‑17D‑204 vaccination, which was well tolerated and induced transient viremia, seroconversion, and functional YF‑specific B‑ and T‑cell responses. This case demonstrates the feasibility of an individualized, immune‑guided approach to safely administering YF vaccination after thymectomy and highlights the need for broader clinical confirmation.

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2018-09-01 | Molecular and clinical relationship between live‐attenuated Japanese encephalitis vaccination and childhood onset myasthenia gravis

Objective The incidence of childhood onset myasthenia gravis (CMG) in China is higher than that in other countries; however, the reasons for this are unclear. Methods We investigated the clinical and immunological profiles of CMG, and assessed the potential precipitating factors. For the mouse studies, the possible implication of vaccination in the pathogenesis was explored. Results In our retrospective study, 51.22% of the 4,219 cases of myasthenia gravis (MG) were of the childhood onset type. The cohort study uncovered that the pathophysiology of CMG was mediated by immune deviation, rather than through gene mutations or virus infections. The administration of the live‐attenuated Japanese encephalitis vaccine (LA‐JEV), but not the inactivated vaccine or other vaccines, in mice induced serum acetylcholine receptor (AChR) antibody production, reduced the AChR density at the endplates, and decreased both muscle strength and response to repetitive nerve stimulation. We found a peptide (containing 7 amino acids) of LA‐JEV similar to the AChR‐α subunit, and immunization with a synthesized protein containing this peptide reproduced the MG‐like phenotype in mice. Interpretation Our results describe the immunological profile of CMG. Immunization with LA‐JEV induced an autoimmune reaction against the AChR through molecular mimicry. These findings might explain the higher occurrence rate of CMG in China, where children are routinely vaccinated with LA‐JEV, compared with that in countries, where this vaccination is not as common. Efforts should be made to optimize immunization strategies and reduce the risk for developing autoimmune disorders among children. Ann Neurol 2018;84:386–400

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2009-11-09 | Safety of influenza vaccination in patients with myasthenia gravis: A population‐based study

Abstract Influenza vaccination has been associated with adverse events including Guillain–Barré syndrome. Because the safety of influenza vaccination in patients with myasthenia gravis (MG) has not been established, some clinicians discourage vaccination for these patients. We explored whether the administration of influenza vaccine to patients with MG might increase the risk of myasthenic crisis. Using population‐based healthcare data from Ontario, Canada, from 1992 to 2007, we utilized the self‐matched, case‐series method of detecting adverse events following vaccination. We studied patients with established myasthenia who were hospitalized for MG within 42 weeks of influenza vaccination. We defined the primary risk interval as the 6 weeks following vaccination. Between January 1, 1992 and March 31, 2006, we identified 3667 hospital admissions for MG. No seasonal trend in MG admissions was evident. In 513 instances, hospitalization occurred within 42 weeks following vaccination in patients previously diagnosed with MG. Among these patients, 266 (52%) were men, the median age was 74 years, and 86 (17%) had previously undergone thymectomy. The estimated relative incidence of admission for MG in the primary risk interval compared with the control interval was 0.84 (95% confidence interval 0.65–1.09). We found similar results in stratified analyses according to gender, age, and thymectomy status. Vaccination of patients with MG against influenza was not found to be associated with exacerbations of the disease. Our findings do not support the practice of withholding influenza vaccination in patients with MG. Muscle Nerve, 2009

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2004-12-01 | Current Issues in the Treatment of Human Diseases by Mucosal Tolerance

A bstract : Tolerance has been defined as a lack of response to self but a more appropriate definition of tolerance is “any mechanism by which a potentially injurious immune response is prevented, suppressed, or shifted to a noninjurious class of immune response.” Thus, tolerance is related to productive self‐recognition, rather than blindness of the immune system to its autocomponents. Oral tolerance, in this sense, is of unique immunologic importance, as it is a continuous natural immunologic event driven by exogenous antigen. Because of their privileged access to the internal milieu, antigens that are continuously in contact with the mucosa are a frontier between foreign and self‐components. Thus, oral tolerance is an immunological mechanism that evolved to treat external agents that gain access to the body via a natural route as internal components that then become part of self. Given this, it would seem logical that autoimmune diseases caused by an inappropriate response to self‐antigens might ultimately be treated by presenting such autoantigens to the mucosal surface where they can be dealt with in a noninjurous (noninflammatory) immunologic environment. Furthermore, mucosal tolerance as a treatment for autoimmune diseases is an attractive concept, as antigen‐specific therapy is the most physiologic means to manipulate immune responses, and mucosal antigen is nontoxic and can be given on a chronic basis. The efficacy of mucosal tolerance has been clearly demonstrated in several animal models.

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2002-06-01 | Therapeutic vaccines: realities of today and hopes for the future

Vaccines are by definition prophylactic, but in recent years an interest has developed in therapeutic vaccines for infectious diseases such as AIDS and tuberculosis, as well as gastric ulcers, cancer (with different approaches to combat various types of malignancy) and autoimmune diseases (a definite success was the development of a vaccine against multiple sclerosis) and there are potential vaccines in development for myasthenia gravis, lupus and diabetes. Therapeutic vaccines are also being developed against cognitive diseases such as Alzheimer's disease, prion diseases and Huntington's disease. All of these efforts are based on the therapeutic vaccine being closely related chemically to the etiological agent that causes the disease.

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other

2024-03-06 | Small extracellular vesicle microRNAs in pediatric myasthenia gravis plasma and skeletal muscle

Abstract Background The diagnosis of myasthenia gravis (MG) in children remains difficult. Circulating small extracellular vesicle (sEV)-derived miRNAs (sEV-miRNAs) have been recognized as biomarkers of various diseases and can be excreted by different cell types. These biomarker candidates also play a vital role in autoimmune diseases via intercellular communication. Methods In the present study, we used sEV isolation and purification methods to extract the plasma-derived sEV-miRNAs from children with MG and healthy controls. A small RNA sequencing analysis confirmed the miRNA expression features in plasma-derived sEVs from MG patients. The miRNA expression analysis in vitro was determined using microarray analysis. The enrichment and network analyses of altered sEV-miRNAs were performed using miRNA databases and Database for Annotation, Visualization, and Integrated Discovery website. Quantitative real-time polymerase chain reaction was performed for validation of sEV-miRNA. The diagnostic power of altered sEV-miRNAs was evaluated using receiver operating characteristic curve analyses. Results Twenty-four sEV-miRNAs with altered expression level were identified between groups by DESeq2 method. The miRNAs were extracted from the sEVs, which were isolated from human primary skeletal muscle cell culture treated with mAb198. The target genes and enriched pathways of sEV-miRNAs partially overlapped between cell supernatant and plasma samples. The significantly downregulated miR-143-3p was validated in quantitative real-time polymerase chain reaction analysis. Conclusions For the first time, we report that plasma-derived sEV-miRNAs may act as novel circulating biomarkers and therapeutic targets in pediatric MG.

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2022-05-24 | [Analysis of clinical characteristics and related genetic variation of juvenile myasthenia gravis].

Objective: To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis (MG) patients. Methods: We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020. After obtaining the patient's informed consent, the blood samples were collected. The Whole Exome Sequencing (WES) was performed on peripheral blood samples. And use biological information software and SPSS 22.0 for data processing and result analysis. Results: According to the inclusion and exclusion criteria, 54 patients with juvenile MG were included, 28 males and 26 females. And the average age of onset was (3.79±0.89) years. Among the enrolled patients, there were 52 (96.3%) patients with ocular MG, the MG-ADL scores of 54 patients were (3.44±0.44) points, and the titer of AChR antibody was (5.88±2.45) nmol/L. Two patients had thymic hyperplasia, and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients, of which TTN gene variants had the largest number, with a total of 17 variants (31.5%). In the TTN gene variant group, 7(41.2%) patients had eye fixation symptoms, and 4 (10.8%) patients in the non-mutation group had eye fixation symptoms. And The difference between the two groups was statistically significant (P=0.016). In addition, the synaptic nucleus envelope protein-1 (SYNE1) and the ryanodine receptor-1 (RYR1) gene variations were also found in 7 cases (13.2%), and no clear relationship between these gene variations and clinical manifestations of MG was found. Conclusions: The incidence of juvenile MG was preschoolers with no gender difference, and ocular MG was more common. The proportion of TTN gene variation in adolescent MG was higher, suggesting that this gene may be a potential therapeutic target for juvenile MG patients. 目的： 分析青少年型重症肌无力（MG）患者的临床特征及相关基因变异特点。 方法： 收集2019年6月至2020年5月在中山大学附属第一医院神经内科就诊的青少年型MG患者的临床资料，征得患者知情同意后留取血标本，应用Illumina平台对血标本进行全外显子检测，运用生物信息软件及SPSS 22.0进行数据处理及结果分析。 结果： 根据纳入和排除标准共纳入54例青少年型MG患者，男28例，女26例，起病年龄（3.79±0.89）岁。入组患者中眼肌型患者52例（96.3%），54例患者的MG-ADL评分为（3.44±0.44）分，AChR-Ab抗体滴度为（5.88±2.45）nmol/L。2例患者合并胸腺增生，5例患者有MG家族史。在54例患者中共发现了169个变异基因，其中肌联蛋白titin（TTN）基因变异例数最多，共发生变异17例（31.5%）。TTN基因变异组中，有7例（7/17）患者有眼球固定表现，非变异组中有4例（10.8%）患者出现眼球固定症状，两组比较差异有统计学意义（P=0.016）。突触核包膜蛋白1（SYNE1）和兰尼碱受体1（RYR1）基因变异共7例（13.2%），未发现此类基因变异与MG临床表现的明确关系。 结论： 青少年型MG的好发人群为学龄前儿童，无性别差异，以眼肌型多见。青少年型MG中TTN基因变异比例较高，提示该基因可能是青少年型MG患者的潜在治疗靶点。.

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2015-12-03 | The African−387 C>T TGFB1 variant is functional and associates with the ophthalmoplegic complication in juvenile myasthenia gravis

Although extraocular muscles are commonly affected by myasthenia gravis (MG) at presentation, a treatment-resistant ophthalmoplegic complication of MG (OP-MG) occurs in younger patients with African-genetic ancestry. In MG, pathogenic antibodies activate complement-mediated muscle damage and this may be potentiated in some OP-MG cases because of relative deficiency of decay-accelerating factor/CD55. Extending this argument, we hypothesized that OP-MG individuals may harbor African-specific polymorphisms in key genes influencing extraocular muscle remodeling. We screened the regulatory region of the transforming growth factor beta-1 (TGFB1) gene encoding the cytokine pivotal in muscle healing responses. We show the frequency of an African-specific polymorphism TGFB1 c.−387 T (rs11466316) among South Africans with African-genetic ancestry is higher than 1000 Genomes African controls (17.2% vs 4.8%; P<1 × 10−7), and associates with juvenile OP-MG (28%; P=0.043). Further, TGFB1 −387 C>T is functional because it represses the TGFB1 promoter construct basal activity by fivefold, and OP-MG fibroblasts (−387 C/T or T/T) have lower basal TGFB1 mRNA transcripts compared with controls (−387 C/C)(P=0.001). Co-transfections with Sp1 show less responsiveness of the −387 T promoter compared with wild-type −387 C (P=0.015). Our findings suggest that population-specific alleles may lower TGFB1 expression, thereby influencing OP-MG susceptibility by inhibiting extraocular muscle CD55 upregulation and/or altered endplate remodeling.

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2015-07-20 | Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease

Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid oligonucleotides generated in vitro based on affinity for certain target molecules by a process known as Systematic Evolution of Ligands by Exponential Enrichment. Aptamers can bind their target molecules with high specificity and selectivity by means of structure compatibility, stacking of aromatic rings, electrostatic and van der Waals interactions, and hydrogen bonding. With several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch to batch variation, flexible modification and stability, lack of toxicity and low immunogenicity, aptamers are becoming promising novel diagnostic and therapeutic agents. This review focuses on the development of aptamers as potential therapeutics for autoimmune diseases, including diabetes mellitus, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus.

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2012-01-24 | CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

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