Search Results (204)

Antibody-mediated autoimmune diseases are common, can involve any organ system, and pose a large burden for patients and healthcare systems. Most antibody-mediated diseases are mediated by IgG antibodies. Selective targeting of pathogenic antibodies is an attractive treatment option which has already proven to be effective in antibody-positive generalized myasthenia gravis, maternal-fetal alloimmune cytopenias, and immune thrombocytopenic purpura. Warm autoimmune hemolytic anemia (wAIHA) is an autoimmune disorder mediated by pathogenic antibodies mainly of the IgG class with no approved therapy. Current treatment includes non-specific immunosuppression with corticosteroids, rituximab, and other immunosuppressive agents. With most therapies, time to response can be delayed and transfusions may be needed. Neonatal Fc receptor (FcRN) therapies provide rapid and sustained reduction of pathogenic IgG levels providing potential for fast, effective therapy in antibody-mediated autoimmune diseases including warm autoimmune hemolytic anemia. This review focuses on the emerging role of FcRn inhibition in autoimmune hematologic diseases, and their therapeutic potential in wAIHA. Full article

Background and Clinical Significance: Neuromyelitis optica (NMO) is a chronic demyelinating inflammatory disease of the central nervous system (CNS), mediated by autoantibodies against aquaporin-4 (AQ4) receptors. In the spectrum of NMO, other autoimmune diseases also coexist, though their association with systemic lupus erythematosus (SLE) is rare. Case Presentation: We present two cases of patients in their 70s who were diagnosed with NMO in the context of SLE. The first case concerns a 78-year-old woman with drug-induced SLE and thoracic myelitis who developed T4-level incomplete paraplegia over three weeks. The second case involves a 71-year-old woman with a history of SLE and myasthenia gravis, presenting with cervical myelitis with progressive worsening of walking and C4-level paraparesis over two months. In both cases, elevated serum anti-AQ4 titers were detected, establishing the diagnosis of NMO and differentiation from an atypical manifestation of SLE-related myelitis. High doses of intravenous corticosteroids with gradual tapering, along with cyclophosphamide, followed by rituximab, were administered in both patients. The first patient showed a poor response, while the second showed improvement. Conclusions: The coexistence of NMO with SLE is rare, but the occurrence of myelitis in patients with connective tissue diseases should raise the suspicion of NMO, especially in elderly women and several years after the diagnosis of SLE. Time to treatment is critical, as delays in treating NMO can result in cumulative and disabling damage. Full article

Background/Objectives: Myasthenia Gravis (MG) and myasthenic syndrome (MSyn) are neurological disorders induced by different types of autoantibodies, characterized by generalized muscle weakness, sometimes involving the respiratory muscles and necessitating ventilatory support. One therapeutic option for severe Myasthenia Gravis (MG) is total plasma exchange (TPE). This procedure reduces the concentration of autoantibodies by extracting the patient’s plasma and replacing it with donor plasma. The TPE efficacy varies among different types of MG, and patient response to TPE is evaluated solely through clinical markers, such as muscle strength. So far, no laboratory method is available for monitoring TPE treatment progress. Objective: In this study, we aimed to determine whether differential scanning calorimetry (DSC) of blood plasma from myasthenic patients is an appropriate tool to monitor and evaluate their condition and the TPE effect. Methods: We performed DSC prior to and after TPE course on blood plasma from three patients with different types of MG: Case 1. Patient with Acetylcholine Receptor Myasthenia Gravis (AChR MG); Case 2. Patient with Muscle-specific tyrosine kinase Myasthenia Gravis (MuSK MG); Case 3. Patient with Myasthenic syndrome (MSyn). Results: DSC thermogram examination revealed increased plasma protein fractions, primarily immunoglobulins (IG), as well as to some extent fibrinogen, relative to a suppressed serum albumin fraction. Successive TPE procedures resulted in IG fraction decline in AChR MG (Case 1) and MSyn (Case 3), and upsurge of the IG fraction in MuSK MG (Case 2). These findings aligned with the clinical presentation of all three cases. Conclusions: DSC revealed distinct, very significant differences in the heat capacity profiles of blood plasma from MG patients relative to healthy controls, as well as strong TPE influence on the plasma thermal behavior. DSC showed promise as a reliable and informative technique for the monitoring of myasthenia and TPE effects across diverse myasthenic patient populations. Further research is needed to confirm and expand on these findings. Full article

Engaging in sports, particularly at a competitive level, requires sustained muscle contractions before the onset of physical fatigue. Fatigue is highly prevalent in neuromuscular diseases, especially those affecting neuromuscular transmission (e.g., myasthenia gravis) or muscle membrane excitability (e.g., myotonia, certain metabolic myopathies). A decremental response in repetitive nerve stimulation (RNS) represents the neurophysiological analogue of exercise-induced muscle weakness. Patients with such responses exhibit abnormal suppression of muscle activity during repetitive or prolonged effort. Consequently, it is often assumed they should avoid strenuous physical activity. To assess the safety of sports participation in individuals with fatigability-related neuromuscular disorders, we examined the literature and report a new case of a patient with myotonia congenita who engaged in competitive sports without adverse events. The review identified only a few cases involving patients with myasthenia gravis or muscular dystrophies who also participated in competitive sports safely and with favorable outcomes. No adverse events were reported. While these findings suggest that sports participation may be feasible for selected patients, they cannot be generalized. Large-scale studies involving athletes with neuromuscular conditions are needed to evaluate the safety and long-term impact of exercise in these populations. Full article

The parathyroid and thymus glands are key components of the endocrine and immune systems, respectively, with intriguing developmental, anatomical, and functional interrelationships. This study starts from the hypothesis that, given their shared embryological origin, it is plausible that the thymus and parathyroid glands interact functionally and may share pathological pathways. The present study explores the developmental pathways, spatial proximity, and potential cross-talk between these glands. Recent studies suggest that parathyroid hormone (PTH) may influence thymic function, including T-cell maturation and immune regulation, while thymic signaling molecules could impact calcium homeostasis and parathyroid activity. Understanding the functional and etiopathogenical relations between these endocrine glands offers new insights into endocrine–immunological crosstalk, and therapeutic approaches targeting disorders such as hypoparathyroidism, thymomas, myasthenia gravis and thymic hypoplasia. Perspectives and conclusion: Future research is essential to discover the molecular mechanisms underpinning this dynamic interrelation and its broader implications for health and disease. Because there is still very little data on this interaction, in-depth studies are necessary on large groups of patients. This research proposes a cross-study of the receptors for the main substances secreted by the two categories of endocrine glands. At the same time, it is essential to carry out an in-depth study on the cervico-pericardial ligaments through the lens of this glandular interaction. These ligaments could contain the main blood and nerve communication pathway between the parathyroids and the glands. Full article

Background: The advent of immunotherapy has revolutionised cancer treatment by harnessing the immune system to target tumour cells. However, there is increasing awareness of immunotherapy-related adverse events, which can be severe and even fatal. While system-specific immune-related adverse events (ir-AEs) are well documented, growing evidence suggests the existence of overlap syndromes—distinct clusters of immune-mediated complications. One such syndrome is the overlap of myasthenia gravis, myositis and myocarditis, collectively known as Triple M (3M) syndrome. This syndrome is complex, varying in presentation and severity, with in-hospital mortality rates approaching 40%. Whilst there is consensus on the management of system-specific complications, there is no consensus guidance for the management of these overlap syndromes. Methods: In this paper, we conduct a review of the literature, analysing reported cases of 3M syndrome, focusing on treatment approaches and patient outcomes at an individual level. Conclusions: This review highlights the complexity of diagnosing and managing 3M syndrome due to inconsistent reporting, lack of standardised criteria for diagnosis, and treatment variability. While evidence remains limited, we offer broad clinical recommendations and underscore the urgent need for consensus definitions, prospective data collection, and structured treatment guidance. Full article

Background/Objectives: Myasthenia gravis (MG) comprises an autoimmune disorder marked by muscle weakness and fatigue. MG frequently coexists with other autoimmune conditions, such as diabetes mellitus, which may exacerbate the clinical burden of MG and adversely impact overall quality of life. Methods: This systematic review and meta-analysis aimed to assess the prevalence of diabetes in patients with MG. Following PRISMA guidelines, a comprehensive search was conducted in the MEDLINE PubMed, Scopus, and Google Scholar databases. Results: A total of 11 studies comprising 16,825 patients were included. The pooled prevalence of diabetes among MG patients was 15.6% (95% CI [8.4%, 24.7%]; I² = 99%, p < 0.001). Compared to healthy controls, MG patients had a 1.24-fold increased risk of developing diabetes (95% CI [1.01–1.54], p < 0.001). Meta-regression showed no association between age and diabetes prevalence, although potential publication bias was noted (Egger’s test, p = 0.72). Conclusions: This meta-analysis reveals a higher prevalence of diabetes among MG patients, with an elevated risk compared to healthy individuals. These findings suggest that the association between MG and diabetes may be mediated by corticosteroid use, genetic factors, and reduced physical activity. The main limitations of this study are the lack of reported data regarding the type of diabetes and patients’ demographic and disease characteristics (MG classification severity and duration and type of treatment). Further studies are needed to investigate the underlying causal mechanisms and to elucidate the relationship between MG and diabetes subtypes. Full article

Background and Objectives: Myasthenia Gravis (MG) comprises an autoimmune disorder marked by muscle weakness and fatigue. MG has been associated with comorbid conditions, including dyslipidemia (DL), which may exacerbate the clinical burden of MG and impact the overall quality of life. Materials and Methods: This systematic review and meta-analysis aimed to assess the prevalence of DL in patients with MG. Following PRISMA guidelines, a comprehensive search was conducted in the MEDLINE, Scopus, and Google Scholar databases. Primary outcomes included the pooled prevalence of DL in MG patients, and the relative risk of DL compared to healthy controls. Results: Nineteen studies involving 98,947 MG patients were analyzed. The pooled prevalence of DL was 23.64% (95% CI: 17.01–30.98). The relative risk of DL in MG patients versus controls was 1.13 (95% CI: 0.53–2.41), indicating no significant increase. Meta-regression revealed a positive correlation between DL prevalence and MG onset age (β = 0.02, p < 0.001), with a 2% rise in DL prevalence per 1-year increase in onset age. Regional subgroup analysis showed a statistical trend of higher DL prevalence in the USA (33.02%) compared to Asia (19.89%) and Europe (17.5%). Conclusions: This study found that approximately one in four MG patients has comorbid DL, with MG onset age significantly influencing DL prevalence. These findings highlight the need for personalized management strategies and evaluations (e.g., statins, LP(a) levels). Further research is warranted to elucidate the pathophysiological links between MG and DL. Full article

Objective: The objective of this retrospective cohort is to analyze survival and other outcomes in patients with myasthenia gravis treated with azathioprine in comparison to the standard treatment based on pyridostigmine and corticosteroids. Methods: A retrospective cohort of 90 patients with myasthenia gravis were followed up on for a mean period of 103.8 months. Survival/mortality was compared between patients receiving azathioprine and those on standard treatment with pyridostigmine and prednisone. Survival analysis was performed with the method of Kaplan–Meier and the Cox proportional hazards model. The long-term side-effects were also reported. Results: The patients on azathioprine had a longer survival according to the unadjusted log-rank test. However, in the multivariate analysis, age at baseline was the only predictor of any cause mortality (HR: 1.12; 95% CI: 1.06–1.19), but not the use of azathioprine (HR: 0.30; 95% CI: 0.10–1.43). Some malignancies appeared in patients treated for more than 10 years. Hematological abnormalities such as leucopenia, anemia, and pancytopenia occurred in four patients and malignancies in three. Conclusions: The use of azathioprine in MG did not result in longer survival compared to standard treatment. Some hematological alterations and malignancies may appear over time in patients receiving azathioprine. Full article

This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of these conditions through the identification and characterization of disease-associated autoantibodies. Disorders such as autoimmune encephalitis, myasthenia gravis, limbic epilepsy, neuropsychiatric systemic lupus erythematosus (NPSLE), and certain forms of schizophrenia have shown clinical responses to immunotherapy, suggesting an underlying autoimmune basis in a subset of patients. The review also highlights the diagnostic relevance of detecting autoantibodies targeting neuronal receptors, such as NMDA and AMPA receptors, or neuromuscular junction components, as biomarkers that guide therapeutic decisions. Furthermore, we synthesize findings from published randomized controlled trials (RCTs) that have validated the efficacy of IVIG and PLEX in specific diseases, such as Guillain–Barré syndrome, and myasthenia gravis. Emerging clinical evidence supports expanding these treatments to other conditions where autoimmunity is implicated. By integrating immunological insights with clinical trial data, this review offers a comprehensive perspective on how immunotherapies may be tailored to target autoimmune contributors to neuropsychiatric disease. Full article

Myasthenia gravis is an antibody-mediated autoimmune condition characterized by defects in cholinergic transmission at the neuromuscular junction. In AchR antibody-positive patients, complement activation plays a prominent role in the disease process, which appears to be mediated by the activation of the membrane attack complex. Since IgG4 is not a good complement activator, the role of complement in MuSK antibody-positive myasthenia gravis patients is negligible. Experimental animal models of myasthenia gravis have shown promise with the antagonism of different elements of the complement cascade, with positive clinical outcomes. This has led to the development of the first C5 inhibitors approved for myasthenia gravis with AchR antibodies: eculizumab, ravulizumab, and zilucoplan. Other clinical trials are currently in progress, investigating the potential therapeutic role of other targets, including the Factor B inhibition or hepatic synthesis of the C5 protein. Other proposed potential targets that have not yet been clinically tested are also discussed in this review article. Full article

Myasthenia gravis (MG) is an autoimmune di sease characterized by muscle weakness. Experimental autoimmune myasthenia gravis (EAMG) serves as an animal model for MG research. Despite advancements in EAMG modeling, limited drug absorption and variability in disease manifestation among animals resulted in a low success rate of model induction. This study aimed to optimize and standardize the modeling process by exploring different induction conditions to improve success rates. We employed female Lewis rats and C57BL/6 mice to compare their sensitivity to model induction and applied a controlled variable approach to acetylcholine receptor (AChR) and H37Ra dosage, mixing time, and injection sites. Results showed that Lewis rats were more suitable than C57BL/6 mice, and 75 µg AChR peptides were more effective than 50 µg. The immune-boosting effect of 1 mg H37Ra Mycobacterium tuberculosis was weaker than 2 mg. While drug mixing time had little impact, increasing injection sites on backs and including foot pads injection, significantly improved drug absorption. Full article

Background: Patients with myasthenia gravis (MG) are susceptible to fractures due to glucocorticoid (GC) use and disease-related functional impairment affecting activities of daily living (ADL). The Fracture Risk Assessment Tool (FRAX^®) estimates fracture probability but does not incorporate disease-specific functional status. We investigated whether combining FRAX^® with the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale improves fracture risk stratification in MG patients. Methods: This single-center prospective cohort study followed 53 MG patients for 10 years (2012–2022) at Toho University Ohashi Medical Center, Japan. Patients were categorized into four groups based on baseline FRAX^® probability (calculated with bone mineral density [BMD]) and MG-ADL scores using median splits: high FRAX^®/high MG-ADL (HH), high FRAX^®/low MG-ADL (HL), low FRAX^®/high MG-ADL (LH), and low FRAX^®/low MG-ADL (LL). The primary outcome was incident major osteoporotic fracture (MOF). Results: Over 10 years, nine MOFs occurred: seven in the HH group (43.8%), two in the HL group (16.7%), and none in the LH or LL groups. Fracture-free survival differed significantly among the groups (log-rank p < 0.001), with the HH group exhibiting the lowest survival rate. Baseline characteristics, including age, disease duration, MG severity scores, BMD, and FRAX^® scores, differed significantly among groups. Specific MG-ADL items reflecting greater impairment (impairment of ability to arise from a chair, double vision, and ptosis) were significantly more pronounced in the HH group at baseline. Conclusions: Combining baseline FRAX^® scores with the MG-ADL assessment effectively stratifies long-term MOF risk in patients with MG. Individuals with both high FRAX^® and high MG-ADL represent a particularly high-risk subgroup. This dual-assessment approach may improve the identification of patients requiring targeted preventive interventions. Full article

Background: Myasthenia gravis (MG) and idiopathic inflammatory myopathy (IIM) are autoimmune diseases that affect the musculoskeletal system. The association of the two diseases is rare. Their management is different, so it is important to recognize the concomitant presentation. Methods: In this cross-sectional study, we study the presence of CK elevation, myositis-specific and myositis-associated antibodies (MSA/MAA), and vitamin D levels in a cohort of 101 MG patients. Electromyography, limb magnetic resonance imaging (MRI), and, in some cases, muscle biopsy were performed when IIM was suspected. We reviewed the patients’ medical records to access the results of these tests if they had been performed previously. Results: CK elevation was detected in 10 patients (9.9%). We identified one case of anti-Jo-1 antibody-positive polymyositis and two cases of possible myositis. MSA/MAA antibodies were not found in the patients with high CK levels, except for the one with anti-Jo-1-positive IIM. One patient with elevated CK levels had an overlapping muscular dystrophy. MSA/MAA antibodies were detected in 19 patients (18.8%). A total of 37% had high-titer antibodies and concomitant systemic autoimmune diseases, while 63% had low-titer antibodies, most of whom had no systemic autoimmune disease. Low serum vitamin D levels were found in 67.3% of patients. Comparison of myasthenia gravis composite (MGC) scores between patients with low and normal vitamin D levels did not show a statistically significant difference. Conclusions: Our results may raise awareness among neuromuscular specialists caring for MG patients of the possibility of associated myositis or other neuromuscular diseases and the need to assess vitamin D levels. Although deficiency was frequent, its impact on MG severity remains unclear, necessitating further investigation into its immunological relevance. Full article

Background and Objectives: Ravulizumab, a long-acting C5 complement inhibitor, was approved in the US and Europe in 2022 as an add-on therapy for the standard treatment of AChR-positive generalized MG (gMG). We share our real-world experience with adult patients receiving this therapy in Romania. Materials and Methods: Six AChR-positive gMG patients received ravulizumab through an Early Access Program (January 2023–October 2024). Patient outcomes were assessed at the therapy start and q8w using Quantitative MG (QMG), MG Activities of Daily Living (MG-ADL), and MG Quality of Life 15-item revised (MG-QoL15r) scales. Results: Age at disease onset ranged from 15 to 35 years. Four of the six patients were women. Two patients had gMG severity level of IIa, and four patients of IIb according to the Myasthenia Gravis Foundation of America (MGFA) classification. Five patients experienced rapid and sustained improvements in MG symptoms with MG-ADL score reductions ranged from −3 to −5 at 26 weeks post-ravulizumab start (except for those with a low baseline score: three and one). QMG score dropped in three patients (−2 to 12) during the treatment period, increased in two (+2 and +8), and remained stable in one (zero). Three patients showed sustained improvement in MG symptoms after ≥60 weeks. MG-QoL15r significantly dropped (−22 to −10) throughout the treatment period. One patient experienced ravulizumab-associated adverse events (vomiting, diarrhea, chills) that resolved within 24 h following symptomatic management, two to three episodes of myasthenic exacerbations during treatment, and discontinued it. Conclusions: All cases presented here had early-onset AChR antibody-positive, non-thymomatous MG. Despite differences in disease duration and underlying conditions, clinically meaningful and sustained improvements in gMG symptoms, and reduced corticosteroid doses were observed in all patients except one after adding ravulizumab to the treatment plan. Full article