Rare adverse events after COVID-19 vaccination among Swedish older adults-evidence from a nationwide register-based study.

Background: One of the most common neuromuscular junction disorders is autoimmune myasthenia gravis (MG). Cytokines profile is expected to be of most important in MG pathogenesis. Objectives: In this research we aimed to analyze serum cytokines profiles in acetylcholine receptor (AChR) antibody positive MG patients and determine the link between these cytokines and clinical parameters of MG. Methodology: Forty AChR antibody positive MG patients and 40 healthy participants (HC) were included in this study. Serum cytokines including IL-2, IL-4, IL-6, IL-15, IL-17 A, IFN-γ, were measured by enzyme linked immunosorbent assay (ELISA). The correlations between serum cytokines levels and clinical profile were analyzed. Results: Serum levels of IL-6, IL-15, IL-17 were significantly higher in MG patients than in HC. Serum levels of IL-4 were significantly lower in MG patients than in HC. According to MG Foundation of America (MGFA) classification, generalized MG group (G-MG) had higher levels of IL-6 and IL-17 than HC, without statistical significant variation among oculomotor MG (O-MG) and HC. We also found that early onset MG (EOMG) had significantly higher IL-2 levels compared to late onset MG (LOMG). We also found significant higher IL-17 levels in thymoma associated MG patients (TMAG) than in MG with normal thymus group. Serum levels of IL-6 and IL 17 were positively correlated with AChR antibodies concentration and quantitative MG (QMG) scores in all MG patients. Conclusion: we can conclude that the pathogenic inflammatory effects exerted by cytokines at neuromuscular junctions are important in MG patients.

The purpose of this study was to explore the composition and function of immune cell subsets at the single-cell level in the thymus and peripheral blood of patients with myasthenia gravis (MG). A total of 9701 and 23 846 cells, respectively, originated from the peripheral blood and thymus samples of two MG patients, and 6930 cells from the peripheral blood of two gender- and age-matched healthy controls (HCs) were selected for single-cell RNA-sequencing. Uniform manifold approximation and projection (UMAP), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Monocle3, and Velcyto were performed to analyze the composition, molecular and functional properties, and developmental trajectory of immune cell subsets. Four major cell populations of T cells, B cells, myeloid cells, and natural killer cells were identified, as well as their 15 cell subpopulations. An absolute predominance of T cells was found in the thymus and peripheral blood of MG patients, and the proportions of memory B cells in both plasma and thymus showed an increasing trend while the number of naïve B cells demonstrated a decreasing trend in MG patients compared with HCs. Besides, the monocytes in the peripheral blood of MG patients had the strongest interactions with other cells. Furthermore, CXCL, GAS, and CD30 signaling pathways were more enriched within MG peripheral blood. Our research clarifies the cellular heterogeneity in the pathogenesis of MG and characterizes the immune microenvironment of thymic tissues in MG patients.

Myasthenia gravis (MG) is a clinically and immunologically heterogeneous autoimmune disease and there is little known about the differential effects of cytokines in disease subgroups. This study aimed to compare serum cytokine profiles across distinct MG subgroups, including early-onset MG (EOMG), late-onset MG (LOMG), muscle-specific kinase antibody-positive MG (MuSK-MG), thymoma-associated MG (TAMG), and healthy controls (HC) in order to distinguish and determine relatively specific targets for the disease subgroups. Serum samples from 22 EOMG, 23 LOMG, 17 MuSK-MG, 25 TAMG patients, and 25 HC were analyzed for a panel of cytokines involved in T and B cell interactions using multiplex bead-based immunoassays and ELISA. Additionally, paired serum samples of the same patients before and after immunosuppressive therapy were evaluated in a subset of patients. IL-17A, IL-4, IFN-γ, IL-21, and IL-9 were significantly elevated in EOMG and MuSK-MG groups, whereas IL-17F, IL-37, IL-2, TNF-α, and IL-13 were higher in EOMG only compared with HC. Increased levels of IL-6 in MuSK-MG and IL-37 in EOMG were found in these subtypes. In contrast, LOMG and TAMG patients showed limited cytokine alterations, with significant increases only in IL-21 in LOMG and IL-17A in TAMG. Immunosuppressive therapy did not significantly alter serum cytokine concentrations. The findings reveal heterogeneous cytokine signatures among diverse MG subgroups, separating EOMG and MuSK-MG from TAMG and LOMG with some similarities and highlighting the impact of age and thymoma presence on immune responses. This assessment of disease subgroups has provided a broader understanding of the cytokines in MG.

Physical activity and sleep influence fatigue in myasthenia gravis (MG), and digital health technologies (DHT) enable objective monitoring of these behaviors in daily life. Using this approach, we evaluated whether a lifestyle intervention targeting physical activity or sleep hygiene could reduce fatigue in MG. In this three-arm, randomized controlled trial (DIG-MG; NCT05992025), 72 MG patients completed 6 weeks of baseline monitoring with a DHT ring (OURA), followed by 12 weeks of (i) physical activity guidance, (ii) sleep hygiene education, or (iii) observation, and a 6-week follow-up. The primary outcome was the MG Activities of Daily Living (MG-ADL) score 1 week postintervention. Secondary outcomes included Fatigue Severity Scale (FSS) scores; exploratory outcomes were DHT-derived physical activity and sleep parameters. Baseline MG-ADL scores were similar (median: 5.0). Postintervention medians were 4.0 (physical activity), 3.5 (sleep hygiene), and 3.0 (control), with no significant differences (p = 0.073). Clinically meaningful MG-ADL improvement occurred in six, seven, and six participants, respectively. FSS scores showed no group differences (p = 0.992), with clinically relevant improvement in eight participants in each intervention group and five controls. Participants were more physically active than expected: 64.7% exceeded 600 MET-min/week at baseline. DHT adherence was excellent. REM sleep was lower than expected, while deep sleep was preserved. Self-reported data aligned with DHT measurements. Digital lifestyle interventions were feasible and well-accepted but did not improve MG-ADL or FSS in this unusually active population. However, DHT-based monitoring may support individualized follow-up, and reduced REM sleep warrants further investigation as a fatigue-related factor.

Juvenile myasthenia gravis (JMG) is a rare autoimmune disease acquired in childhood, comprising 8%-15% of all myasthenia gravis cases depending on geographic and ethnic populations. Ocular myasthenia gravis presents as ptosis with extraocular movement restriction and is frequently misdiagnosed as third nerve palsy or congenital ptosis when bilateral. Early diagnosis prevents disease progression and unnecessary interventions. We report a case of JMG initially misdiagnosed as Guillain-Barré syndrome (GBS) to highlight diagnostic pitfalls. A 4-year-old girl presented with left eye ptosis, followed by bilateral ptosis after 2 days, then gait disorder and inability to stand after 5 days. She had a previous admission 2 months earlier with severe respiratory distress, for which she received intravenous immunoglobulin (IVIG) under the suspicion of GBS. In the current admission, bilateral ptosis was evident, and repetitive nerve stimulation (RNS) showed a decremental response of > 10%, consistent with myasthenia gravis. Anti-acetylcholine receptor (AChR) antibody was positive. She was treated with pyridostigmine (5 mg/kg/day) and showed good response. JMG should be considered in the differential diagnosis of acute muscle weakness with cranial nerve involvement, even when respiratory failure dominates, and normal cerebrospinal fluid protein in suspected GBS should prompt re-evaluation.

Fatigue is a common, often disabling symptom in myasthenia gravis (MG), distinct from muscle fatigability, and strongly associated with reduced quality of life. This narrative review examines current evidence on fatigue in MG, its patient impact, and future research directions. Earlier studies, mostly small and heterogeneous, reported a highly variable prevalence of fatigue. Recent large registry-based studies have now established a more consistent prevalence around 60% and confirmed associations with disease severity, depressive symptoms, and physical inactivity. Fatigue has also been assessed as secondary endpoint in phase 3 trials of targeted immunotherapies, with improvements paralleling broader clinical benefits. In contrast, non-pharmacological approaches remain understudied; however, several studies have recently been initiated in which fatigue is a predefined outcome measure. Emerging biomarker evidence suggests that systemic low-grade inflammation may contribute to fatigue. Together, these insights highlight the need for targeted, multidimensional strategies to better understand and treat fatigue in MG.

Checkpoint inhibitors, a class of immunotherapeutic agents, have transformed the oncology landscape by targeting immune checkpoints - regulatory pathways that modulate immune cell activity. By inhibiting proteins such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), these agents enhance the immune response against cancer cells. However, their efficacy comes at the cost of a range of immune-related adverse events (irAEs), including autoimmune reactions such as colitis, hepatitis, and endocrinopathies, which can range in severity from mild to life-threatening. We present the case of a 76-year-old man with cholangiocarcinoma on durvalumab, a PD-L1 inhibitor, who presented to the emergency department with shortness of breath, cough, and weakness. Workup led to the diagnosis of immune-related myasthenia gravis and a non-ST-elevation myocardial infarction (NSTEMI), the latter believed to be secondary to durvalumab-induced myocarditis. Initial treatment with intravenous immunoglobulin (IVIG) produced brief, partial symptomatic improvement but failed to resolve respiratory weakness or other bulbar manifestations. His condition deteriorated rapidly, progressing to respiratory failure within weeks of onset. Given the refractory nature of his disease course, he was subsequently treated with a repeat dose of IVIG and prednisone, then transferred to an outside facility for plasma exchange. Despite these interventions, the patient ultimately succumbed to his illness. This case highlights the rare but potentially fatal concurrent occurrence of immune-related myasthenia gravis and myocarditis as irAEs in a patient receiving durvalumab for cholangiocarcinoma. While checkpoint inhibitors have revolutionized outcomes across many solid tumor malignancies, this case underscores the diagnostic and management challenges posed by severe, refractory irAEs, and the importance of early recognition and aggressive treatment in this patient population.

Immune-related markers define clinically relevant prognostic subgroups in thymic epithelial tumors.

Neuromuscular junction (NMJ) disorders such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism are characterized by impaired synaptic transmission leading to weakness. This review examines the electrodiagnostic evaluation of these conditions, emphasizing the importance of techniques such as repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) for confirming the diagnosis and distinguishing presynaptic from postsynaptic defects. The reduced safety factor of neuromuscular transmission (NMT) in postsynaptic disorders produces a decrement in compound muscle action potential (CMAP) amplitude and area with low-frequency stimulation, whereas presynaptic disorders show small baseline CMAPs that increase markedly in amplitude and area (postactivation facilitation) after brief exercise or during high-frequency stimulation. SFEMG, the most sensitive test of abnormal NMT, measures neuromuscular jitter-temporal variability in action potential generation-and also reflects a compromised safety factor. Fiber density remains normal in primary NMJ disorders, distinguishing them from conditions with neuropathic reinnervation, such as motor neuron disease. Proper performance and interpretation of these electrodiagnostic studies are essential for accurate diagnosis, assessment of disease severity, and guiding management of NMJ disorders.

Chimeric antigen receptor-based cellular therapy in autoimmune diseases: A systematic review and meta-analysis of clinical, serological and safety outcomes.

The management of patients with generalized myasthenia gravis (gMG) is complex and often involves substantial health care expenses. As the treatment paradigm continues to evolve, understanding the economic burden of gMG must also reflect the availability and increasing use of newly approved and advanced therapies in a diverse patient population. To estimate incremental health care resource utilization (HRU) and costs associated with gMG compared with non-MG controls and identify predictors of high health care costs in gMG in an insured US population cohort. Adults with newly diagnosed gMG were identified from Komodo Research data (January 1, 2017, to September 30, 2023). Characteristics of adults without MG were weighted using entropy balancing to match the gMG cohort. The index date was the first MG diagnosis by a neurologist for the gMG cohort and a random date for the non-MG cohort. Annual per patient HRU and health care costs were compared between the weighted cohorts. Predictors of high health care costs were evaluated among the gMG cohort using a logistic regression model. After weighting, among 6,195 patients in the gMG cohort and 226,008 in the non-MG cohort, the mean age was 61.1years, 49.1% were female, 53.4% were covered by commercial insurance, 41.0% were covered by Medicare Advantage, and 5.6% were covered by Medicaid. The gMG cohort (mean follow-up = 32.7 months) compared with the non-MG cohort (mean follow-up = 31.3 months) had 2.4, 1.6, and 1.9 times more inpatient days, emergency department visits, and outpatient visits annually, respectively (all P < 0.001). Mean annual all-cause total health care costs in the gMG cohort were $43,872 higher than in the non-MG cohort ($58,341 vs $14,469; P < 0.001); 59.3% of the difference was driven by pharmacy costs (mostly immunoglobulin). Prediagnosis weakness and fatigue symptoms, exacerbation or crisis, and use of immunoglobulin were important factors significantly associated with high health care costs in the gMG cohort (all P < 0.001). Despite advances in treatment, the economic burden of gMG remains substantial. Association of high health care costs with early symptoms and disease exacerbations underscores the need for more effective intervention strategies to improve disease control and reduce HRU and costs in patients with gMG.

The burden of myasthenia gravis (MG) is often underestimated, and studies usually focus on the symptom burden. However, treatment-related adverse events also contribute to patients' burdens and affect their treatment decisions. Understanding the treatment preferences of people with MG will help inform patients, clinicians, and policy makers. We conducted a qualitative study to understand the most relevant factors that people with MG consider when making treatment decisions. Fifteen patients with a wide range of MG severity participated in semi-structured interviews. Interviews were recorded and transcripts were analyzed using line-by-line open coding to generate themes. We used these themes to identify the most relevant treatment characteristics for people living with MG. Four themes were identified: MG symptoms, treatment side effects, treatment delivery preferences, and treatment goals. Double vision was the most bothersome symptom for 40% of patients, and 33% reported weight gain as the most bothersome side effect of treatment. Most patients preferred treatments in the form of pills (67%). The most frequently reported treatment goals were returning to normal or "zero symptoms" (40%), discontinuation of prednisone (40%), and a preference to take fewer pills (33%). Our results underscore the importance of tailoring treatments to meet patient needs and preferences, emphasizing key treatment goals such as prednisone reduction, a preference for oral medications, and symptom resolution. We will incorporate these themes into a discrete choice experiment to gain a deeper understanding of how people with MG make treatment decisions when considering potential benefits and adverse events.

Mindfulness-based interventions (MBIs) are increasingly studied for clinical conditions, with evidence pointing toward their benefits for chronic and autoimmune disorders. Research shows the biological effect of MBIs on immunological pathways and benefits for fatigue, mood, and quality of life in chronic conditions. These raise the possibility of benefits in myasthenia gravis (MG). However, there is a gap in research on MBIs for MG. This paper makes the case for MG research to study the potential benefits, mechanisms, and special considerations when designing MBIs for people living with MG. Suggestions are offered on the use of mindfulness practices for MG based on the author's experience.

A cure for myasthenia gravis is necessary to achieve "A World Without Myasthenia Gravis". Current treatments reduce symptom burden and broadly suppress immune activity, but generally need to be administered chronically and are associated with significant risks, incomplete remission rates, infrequent treatment-free remission, and potential disability. We define a cure for MG as complete remission of MG, without the need for ongoing treatment, plus desirably: a high probability of success; a low risk of later relapse; the possibility of treatment repetition if MG does relapse; low and proportionate treatment toxicity; and cost-effectiveness. Thymectomy is the only currently available widely applied sometimes curative treatment for ACHR+ antibody MG. The MGTX trial post hoc analysis showed a 52% steroid free remission rate following thymectomy, which is approximately 1/3 of the whole population above the background remission rate. However, thymectomy is not universally applied even in younger ACHR+ patients. Recent regulatory approved and marketed therapies for MG are highly effective but are largely chronic continuous suppressive strategies at significant cost. Non-selective ablative chemotherapy and transplant or CAR-T approaches to B or plasma cells in development have toxicity risks and may still require maintenance therapies to prevent relapse. Treatments specific only to the pathogenic antibodies or clones using antigen-bait, anti-idiotype, or toleragenic approaches are yet to be demonstrated in humans with spontaneously acquired myasthenia gravis. A cure for myasthenia gravis remains an unmet need.

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

Generalized myasthenia gravis (gMG) is a chronic autoimmune disorder that causes muscle weakness. This human factors (HF) validation study aimed to demonstrate that use of a prefilled syringe with needle safety device (PFS-SD) or autoinjector (AI) is safe and effective for patients with gMG, caregivers, and healthcare professionals (HCPs) to administer injectable medication in the intended use environments without preventable use errors. Patients with gMG, caregivers, and HCPs were randomized to the PFS-SD or AI. No training on either device use was provided. The safety and usability of both devices were assessed using simulated use scenarios, knowledge-based questions, and participant feedback. The simulated use scenario was successfully completed by 94% and 96% of participants using the PFS-SD and AI, respectively, while 90% and 87% of participants, respectively, successfully administered their assigned dose. Device acceptability was reported by 93% and 100% of patient participants for the PFS-SD and AI, respectively. This HF validation study demonstrated that the PFS-SD and AI are safe and effective for use by patients with gMG, caregivers, and HCPs in the intended use environments.

Muscle-specific kinase myasthenia gravis (MuSK-MG) is an autoimmune neuromuscular disorder predominantly mediated by IgG4 autoantibodies disrupting MuSK signaling. The contribution of other isotypes remains incompletely defined. We characterized the serological profile of a Greek cohort of MuSK-MG patients. Baseline (n = 140) and longitudinal (available n = 99) samples from 140 patients, positive for anti-MuSK by radioimmunoprecipitation (RIPA) were analyzed using a live cell-based assay (L-CBA) to detect total IgG, IgG1-4 subclasses, IgM, and IgA. Also, disease and healthy controls (n = 102) were included. Selected samples were additionally analyzed by flow cytometry. Clinical data were available for specific patients. Our analysis revealed 15 distinct immunoglobulin combinations and provided insights into the presence of IgA isotype. IgG4 was the most common subclass in 120/140 of patients, followed by IgG1 in 79/140, IgG3 in 59/140, and IgG2 in 42/140 patients, while IgM positivity was detected in selected patients. Anti-MuSK IgA(1) immunoreactivity was detected in 54/140 patients, frequently co-occurring with IgG, and in four patients at baseline with only-IgA positivity. IgA was detected both near disease onset and at later stages, and persisted over time in rituximab-treated patients. Controls tested largely negative for IgA, although low-intensity signals were observed in six samples and were considered non-specific. L-CBA detected anti-MuSK IgA more frequently than flow cytometry. Our findings expand the serology of MuSK-MG beyond IgG subclasses, identifying IgA as an additional component of the anti-MuSK response. These results enhance further investigation into the clinical significance, pathogenic potential, and treatment-associated fluctuations of anti-MuSK IgA antibodies.

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.

Oral corticosteroids remain a cornerstone of therapy for generalized myasthenia gravis (gMG) but are associated with substantial long-term toxicity. Efgartigimod, a human immunoglobulinG1 (IgG1) antibody Fc fragment targeting the neonatal Fc receptor (FcRn), has demonstrated efficacy in gMG; however, no prospective trial has evaluated whether regularly scheduled efgartigimod administration can safely reduce oral prednisolone (PSL) dosage. We designed a prospective clinical study to evaluate the steroid-sparing effect of efgartigimod in patients with gMG who remain dependent on ≥ 6mg/day of oral PSL. This is a single-arm, open-label, single-center clinical study. Patients with gMG who are receiving ≥ 6mg/day of oral PSL on a stable dose for at least 4weeks prior to enrollment, with any concomitant oral immunosuppressants also at stable doses for at least 4weeks, and scoring ≥ 5 on the MG Activities of Daily Living (MG-ADL) scale will be enrolled. Efgartigimod will be intravenously administered at 10mg/kg once weekly for 4 consecutive weeks (one cycle), repeated for four cycles with a 28-day interval between cycles. On the fourth administration day of each cycle, oral PSL will be tapered if MG symptoms have not worsened, defined as no ≥ 1-point increase in the MG-ADL score from both baseline and the first administration day of that cycle. The primary endpoint is the change in PSL dosage from baseline at the end of the study. Secondary endpoints include the proportion of patients achieving minimal manifestations (MM) or better status with PSL ≤ 5mg/day (MM-5mg), the time to reach ≤ 5mg/day, the cumulative PSL dose over the study period, the proportion of patients completing the protocol, changes in MG-ADL and other clinical scales, responder rate to efgartigimod, comparison of clinical course between MG subtypes (anti-acetylcholine receptor (AChR) antibody-positive, anti-muscle-specific kinase (MuSK) antibody-positive, and double-seronegative cases) and between patients who are anti-AChR antibody positive, with and without thymoma, changes in indicators of steroid toxicity (HbA1c, lumbar spine bone mineral density, and blood pressure), and the safety profile. The study will also explore biomarkers predictive of efgartigimod response through proteomic and immunologic analyses of serially collected blood samples. Graphical abstract available for this article. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT), CRB3180028; registered on 1 October 2024 (prospectively registered).