Anti-acetylcholine Receptor Antibody Levels Research Articles

Neonatal Fc receptor (FcRn)-A Novel Therapeutic Approach for Autoimmune Disease

Neonatal Fc receptor (FcRn) is involved in recycling of IgG. Recycling begins with IgG-uptake into the cell through pinocytosis. Subsequently, IgG binds to FcRn in acidic vesicles, which results in the recycling of the FcRn-IgG complex to cell surface, and the release of IgG in blood with neutral pH. Whereas IgG unbound to FcRn is not recycled and thus degraded in lysosomes. Therefore, FcRn plays a critical role in maintaining IgG levels in the blood. Recently, FcRn has been considered a therapeutic target for autoimmune diseases caused by IgG autoantibodies, and FcRn inhibitors are developed as therapeutic agents for the diseases. As one example, the administration of an FcRn inhibitor, efgartigimod, reduced IgG and anti-acetylcholine receptor antibody levels in patients with generalized myasthenia gravis (gMG), and improved Myasthenia Gravis Activities of Daily Living score in the phase III trial. In 2022, Efgartigimod Alfa was approved for the treatment of gMG (only when treatment with steroids or non-steroidal immunosuppressive drugs do not lead to sufficient response), regardless of antibody status in Japan. Since FcRn inhibitors have just begun to be used in clinical practice, it is important to accumulate real-world data regarding their efficacy and safety. (Received August 21, 2023; Accepted October 6, 2023; Published February 1, 2024).

Ophthalmologic Manifestations of Ocular Myasthenia Gravis

Purpose: We investigated the ophthalmic manifestations observed in patients diagnosed with ocular myasthenia gravis.Methods: In total, 58 patients diagnosed with ocular myasthenia gravis visited the ophthalmology and neurology departments between January 2011 and August 2022. Patients were followed for > 6 months; their ophthalmic manifestations were analyzed retrospectively.Results: The study included 29 males and 29 females with a mean age of 55.52 ± 15.60 years. Among the patients, 31 tested positive for anti-acetylcholine receptor antibodies, resulting in a positive rate of 53.45%. Abnormalities in repeated nerve stimulation tests were observed in 33.33% of the patients. The antibody-positive group exhibited a higher frequency of progression to generalized myasthenia gravis (p = 0.011) and a higher incidence of chest abnormalities (p < 0.001) compared to the antibody-negative group. Horizontal and vertical diplopia were commonly observed in a complex group of patients with diplopia and blepharoptosis (p < 0.001); there was a difference in the pattern of strabismus between the diplopia single group with esotropia and the complex group with exotropia (p = 0.029). In addition, the combination group demonstrated a higher antibody titer (p = 0.034), a higher frequency of abnormalities in repeated nerve stimulation tests (p = 0.022), and a higher incidence of chest abnormalities (p = 0.022).Conclusions: The anti-acetylcholine receptor antibody-positive group had a higher incidence of progression to generalized myasthenia gravis; moreover, the complex group of patients with diplopia and ptosis exhibited elevated levels of anti-acetylcholine receptor antibodies and frequently accompanied both horizontal and vertical strabismus.

P06.19.A BEYOND T CELL TOXICITY - INTRATHECAL CXCL13 ELEVATION INDICATES B-CELL INVOLVEMENT IN NEUROLOGICAL IMMUNE-RELATED ADVERSE EVENTS FOLLOWING IMMUNE CHECKPOINT INHIBITION: 2 CASE OBSERVATIONS AND COMPREHENSIVE REVIEW

Abstract BACKGROUND Neurological immune-related adverse events (nirAE) can occur following cancer treatment with immune checkpoint inhibitors (ICI). Mainly attributed to autoreactive T-cells, nirAE usually respond to first line therapy with high-dose steroids (GC). Severe or fatal outcomes are rare & most frequently reported in clinically overlapping syndromes with accumulating evidence of B cell autoimmunity. MATERIAL AND METHODS We present 2 patients who developed grade 3-4 nirAE with evidence suggestive for B cell involvement. RESULTS Case 1: A 75y female with metastatic melanoma developed double vision & general weakness 2 weeks after the 1st cycle of ipilimumab & nivolumab. Diagnostic workup showed pleocytosis (27 cells/µl) with elevated CXCL13 (316 pg/ml) in cerebrospinal fluid (CSF). Increases of creatine kinase, troponin T, elevated levels of anti-acetylcholine receptor antibodies & positive anti-titin antibodies led to the diagnosis of myocarditis & myositis/myasthenia gravis overlap syndrome. The patient received pulsed high-dose GC with tapering. CSF flow cytometry revealed intrathecal recruitment of CXCL13-responsive B cell helper T cells of a predominant inflammatory phenotype & a highly increased pathological CD4/CD8 T cell ratio in peripheral blood. Clinically non-responding to GC, the patient received additional therapy with immunoglobulins (IVIG). 2 weeks later she was readmitted due to generalized myopathy with dropped head & received a second cycle of high-dose GC since she refused plasmapheresis. Further escalation with rituximab could not be realized because the patient rapidly deteriorated & deceased. Case 2: A 75y female with metastatic invasive enteric adenocarcinoma of the lung developed gait ataxia & ataxia of the lower limbs 5 months after pembrolizumab therapy. CSF analysis showed a pleocytosis (248 cells/µl) with plasma cells, pronounced CXCL13 elevation (>488 pg/ml) & positive screening for anti-neuronal cerebellar antibodies, suggesting ICI-mediated cerebellitis. The patient received high-dose GC & IVIG for 5 days each, was discharged but readmitted 5 months later due to subacute onset of spastic paraparesis. Magnetic resonance imaging of the spine revealed thoracic myelopathy & CSF showed mild pleocytosis (5 cells/µl), intrathecal immunoglobulin synthesis & mild CXCL13 elevation (33 pg/ml). The patient completed a second cycle of steroids followed by rituximab targeting B-cell involvement & currently 4 months later is clinically stable. CONCLUSION Intrathecal CXCL13 may serve as diagnostic tool of B cell involvement, here supported by intrathecal immunoglobulin synthesis, presence of plasma cells and/or severely altered immune cell compositions. Early treatment escalation with B cell depleting agents such as rituximab may help prevent fatal clinical courses.

Nivolumab-related myasthenia gravis with myositis requiring prolonged mechanical ventilation: a case report

BackgroundNivolumab is an immune checkpoint inhibitor that blocks inhibitors of T-cell activation and blunts antitumor immunity and is used in the treatment of various cancers. However, immune checkpoint inhibitors have immune-related adverse effects on various organs due to promoting T-cell activity against host tissues by blocking inhibition of T-cell function. Although immune-related adverse effects including hepatitis, colitis, pneumonitis, dermatitis, nephritis, endocrinopathies, and hypophysitis are well recognized with established treatment guidelines, neuromuscular immune-related adverse effects are rare phenomena.Case presentationA 55-year-old Asian (Japanese) woman was diagnosed with nivolumab-related myasthenia gravis with myositis and myocarditis. She had a past history of thymectomy for large thymoma with a high anti-acetylcholine receptor antibody level without any symptoms. Nivolumab was administered for the treatment of malignant melanoma. Creatine kinase levels began to rise 2 weeks after the administration, and abnormal neurological findings appeared 3 weeks after the administration. Ventricular arrhythmia, wide QRS complex, and dyssynchrony of the left ventricle also appeared. Intravenous immunoglobulin and corticosteroids were administered, and plasma exchange was performed. The patient required intensive care and prolonged mechanical ventilation with tracheostomy owing to weakness of the diaphragm; she was eventually weaned from the ventilator and discharged. Diaphragm ultrasound was used for the decision-making of the weaning strategy and evaluation of the diaphragmatic function.ConclusionsNivolumab-induced severe myasthenia gravis with myositis and myocarditis required intensive care and prolonged mechanical ventilation. Although immune checkpoint inhibitor-related myasthenia gravis is a rare adverse event, appropriate and prompt treatment is required because of its severity and rapid progression. Diaphragm ultrasound was useful not only in diagnosing diaphragm dysfunction and deciding the strategy for weaning from mechanical ventilation but also in evaluating the recovery of the diaphragmatic function.

Risk factors for developing post-thymectomy myasthenia gravis in patients with thymoma.

Thymectomy is required for the treatment of thymoma-associated myasthenia gravis (MG). However, MG may develop only after thymectomy, a condition known as post-thymectomy MG. This study aimed to investigate the risk factors for post-thymectomy MG in patients with thymoma. We retrospectively identified 235 patients with thymoma who underwent thymectomy at a single hospital from January 2008 to December 2017: 44 with preoperatively diagnosed MG were excluded, leaving 191 patients in the final analysis. Univariable survival analyses using Cox proportional hazards regression model and Kaplan-Meier estimate were conducted to identify risk factors for post-thymectomy MG. Post-thymectomy MG developed in 4.2% (8/191) of the patients with thymoma between 18 days and 108 mo after surgery. Hazard ratios (HRs) of pre- and postoperative anti-acetylcholine receptor antibody (AChR-Ab) titers were 2.267 (P = .002) and 1.506 (P < .001), respectively. Patients with extended thymectomy had a low chance of post-thymectomy MG (HR 0.035, P = .007). Larger thymoma (HR, 1.359; P = .005) and type A or AB thymoma according to World Health Organization histological classification (HR, 11.92; P = .021) were associated with higher chances of post-thymectomy MG. Within the subgroup of preoperatively AChR-Ab seropositive patients, post-thymectomy MG developed in 22.2% (6/27). Pre- and postoperative AChR-Ab levels should be measured in patients with thymoma. A large thymoma and partial thymectomy appear to be associated with a higher probability of post-thymectomy MG.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study

BackgroundMyasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis.MethodsPatients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic.ResultsA total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161).ConclusionsJuvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

P3.CR-31 A Case of Thymoma with Autoimmune Hepatitis Following Preoperative Chemotherapy

We encountered a case of thymoma with autoimmune hepatitis. A 63-year-old woman was found to have an abnormal finding on chest radiography during a medical checkup, but did not seek further care. She was referred to our hospital one year later when a bilateral hilar abnormality was again found during a checkup. Chest computed tomography (CT) showed a 4.6 × 3.0 × 5.6 cm mass with calcifications in the anterior mediastinum. The tumor invaded the right lung and middle lobe, in association with a 2.0-cm daughter nodule in the head of the main tumor, with multiple pleural seeding lesions in the right thoracic cavity. Although she was asymptomatic, the anti-acetylcholine receptor antibody level was elevated to 33 nmol/L and the soluble IL-2 receptor antibody was elevated to 1,700 U/mL. The mass was diagnosed with CT-guided biopsy as a type-B2 thymic tumor (cT3N0M1a, c-Stage IV). She underwent induction chemotherapy (ADOC, 2 courses). After chemotherapy, abnormal liver enzyme levels (aspartate aminotransferase: 451 U/L, alanine aminotransferase: 529 U/L) were noted on preoperative examination. She was diagnosed with autoimmune hepatitis based on liver biopsy findings and treated with oral prednisolone 30 mg. Surgery was performed after prednisolone dose was gradually decreased to 20 mg. Extended thymectomy and pulmonary wedge resection using median sternotomy were performed. Pleural dissemination was resected using video-assisted thoracoscopic surgery. The pathological findings showed type-B3 thymic carcinoma (pT3N0M1a, p-Stage IV, Masaoka classification IVa). She was placed under observation without any additional treatment. Prednisolone dose has been gradually decreased to 15 mg without exacerbation of liver function. The anti-acetylcholine receptor antibody level decreased after surgery. Autoimmune diseases in association with thymoma are well known, but reports of autoimmune hepatitis are very rare. Autoimmune hepatitis must be considered when acute liver damage is observed.

Anterior mediastinal tissue volume is correlated with antiacetylcholine receptor antibody level in myasthenia gravis

ObjectivesExtended thymectomy is a treatment option for myasthenia gravis (MG), but the surgical indications are controversial. Pathologic features of the thymus can be used to predict surgical outcomes, but there is no reliable method for evaluating these characteristics preoperatively. The purpose of this study was to determine whether anterior mediastinal tissue volume, as measured via 3-dimensional computed tomography (3DCT) volumetry, correlates with serum anti-acetylcholine receptor antibody (AChRAb) levels in patients undergoing thymectomy for myasthenia gravis. Therefore, we investigated the relationships among anterior mediastinal tissue volume determined by 3DCT volumetry and AChRAb levels. MethodsThe subjects were 28 patients who underwent extended thymectomy and were enrolled retrospectively. We measured volume of the anterior mediastinum and calculated the volumes of more than −30 Hounsfield units (V−30) by using 3DCT volumetry and compared them with perioperative AChRAb levels. The significance of their volumes in MG was examined by comparison with 53 patients without MG. ResultsV−30 values were related to age and were significantly greater in patients with MG than in patients without MG (P < .001). V−30 values were correlated positively with preoperative AChRAb levels (ρ = 0.505, P = .006) and inversely with the post/preoperative AChRAb ratio (ρ = −0.453, P = .018). The histologic nonadipose tissue ratio was correlated with the V−30/volume of the anterior mediastinum (ρ = 0.700, P < .001). ConclusionsThis method for evaluation of the anterior mediastinal tissue volume and AChRAb production may be helpful in establishing a treatment plan for MG.

抗アセチルコリンレセプター抗体高値を伴った赤芽球癆合併胸腺腫の1例

胸腺腫は様々な免疫疾患を合併する．今回われわれは，抗アセチルコリンレセプター抗体（以下抗AChR抗体）高値を伴った赤芽球癆合併胸腺腫の1例を経験したので報告する．症例は61歳の女性．検診で胸部異常影を指摘され当院受診．胸部造影CT検査で前縦隔に約6cm大，均一な造影効果を伴う境界明瞭な腫瘤影を認め，胸腺腫疑いと診断されたほか，網状赤血球数低下を伴う正球性正色素性貧血を認め，骨髄検査で赤芽球癆と診断．抗AChR抗体高値も認めたが，臨床的に重症筋無力症の症状を認めず．胸腺腫に対する拡大胸腺摘出術を施行後，経過良好で第10病日退院．病理所見では胸腺腫（WHO分類typeAB，正岡分類II期）と診断．約1カ月後より再び貧血の進行を認めたため，免疫抑制剤（シクロスポリン）による治療を開始．1週間後より貧血に改善傾向が見られ，以後，輸血非依存の状態を維持しており，重症筋無力症の症状も顕在化していない．

Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis

Thymectomy plays an important role in patients with myasthenia gravis (MG). This study aimed to explore predictors of postoperative myasthenic crisis (POMC) after thymectomy and to define a predictive score of respiratory failure. The clinical data of 177 patients with MG undergoing thymectomy from January 1995 to December 2011 were retrospectively reviewed. The following factors were analysed in relation to the occurrence of myasthenic crisis: gender, age, body mass index (BMI), anti-acetylcholine receptor-antibody level, bulbar symptoms, comorbidities, duration of symptoms, Osserman-stage, Myasthenia Gravis Foundation of America (MGFA) stage, history of myasthenic crisis, use of immoglobulins or plasmapheresis, kind of therapy, spirometric and blood gas parameters, histology, kind of surgery, non-myasthenic complications and duration of intubation. Twenty-two patients experienced postoperative respiratory failure after thymectomy. Univariate analysis revealed a correlation with age >60 years (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.04-6.78; P = 0.040); Osserman-stage (IIB- OR = 5.16, 95% CI = 1.10-24.18; P = 0.037, III-IV- OR = 8.75, 95% CI = 1.53-50.05; P = 0.015); bulbar symptoms (OR = 7.42, 95% CI = 1.67-32.84; P = 0.008); BMI >28 (OR = 3.99, 95% CI = 1.58-10.03; P = 0.003); preoperative plasmapheresis (OR = 2.97, 95% CI = 1.18-14.04; P = 0.021); duration of symptoms >2 years (OR = 4.00, 95% CI = 1.09-14.762; P = 0.036); extended surgery (OR = 2.52, 95% CI = 1.02-6.22; P = 0.045); lung (OR = 4.05, 95% CI = 1.44-11.42; P = 0.008), pericardial (OR = 3.78, 95% CI = 1.45-9.82; P = 0.006) or pleural resection (OR = 3.23, 95% CI = 1.30-8.03; P = 0.012); Vital Capacity % <80% (OR = 0.20, 95% CI = 0.05-0.82; P = 0.025) and PaCO2 >40 mmHg (OR = 3.76, 95% CI = 1.12-12.68; P = 0.032). Multivariate logistic regression analysis showed that Osserman-stage (IIB- OR = 5.69, 95% CI = 1.09-29.69; P = 0.039 (III-IV- OR = 11.33, 95% CI = 1.67-76.72; P = 0.013), BMI >28 (OR = 3.65, 95% CI = 1.10-12.15; P = 0.035), history of myasthenic crisis (OR = 24.10, 95% CI = 2.34-248.04; P = 0.007), duration of symptoms >2 years (OR = 5.94, 95% CI = 1.12-31.48; P = 0.036) and lung resection (OR = 8.48, 95% CI = 2.18-32.97; P = 0.002) independently predict POMC. Excluding history of preoperative myasthenic crisis (statistically associated with Osserman-stage), we built a scoring system according to the OR of Osserman-stage (I-IIA, IIB, III-IV), BMI (<28, ≥ 28), duration of symptoms (<1, 1-2, >2 years) and association with a pulmonary resection. This model helped in creating four classes with increasing risk of respiratory failure (Group I, 6%; Group II, 10%; Group III, 25%; Group IV, 50%). Our model facilitates the stratification of patient risk and prediction of the occurrence of POMC. Moreover, it could help to guide the anaesthesiologist's decision on the duration of intubation. Further studies based on larger series are needed to confirm these preliminary data.

Allogeneic Hematopoietic Cell Transplantation for Refractory Myasthenia Gravis

To describe a patient with intractable myasthenia gravis (MG) who was treated with a matched sibling peripheral blood stem cell transplantation. Case report. Patient A 17-year-old boy with MG diagnosed at 11 months of age who was previously treated with pyridostigmine, intravenous immunoglobulin, corticosteroids, thymectomies, azathioprine, mycophenolate mofetil, plasmaphereses, rituximab, and high-dose cyclophosphamide. The patient underwent a reduced-toxicity conditioning with intravenous busulfan, fludarabine, and alemtuzumab, followed by a peripheral blood stem cell infusion from his HLA-matched sibling. Before transplantation, the patient was receiving frequent plasmaphereses, intravenous immunoglobulin, and pyridostigmine. He had ophthalmoplegia, oropharyngeal and limb muscle involvement, and limited mobility. At 40 months posttransplantation, his oropharyngeal and skeletal muscle weakness has completely resolved, he is not taking any medications for MG, and he is an avid athlete. However, his ophthalmoplegia persists, and his anti-acetylcholine receptor antibody levels remain elevated. Following allogeneic hematopoietic stem cell transplantation, the presence of anti-acetylcholine receptor antibodies was not sufficient for inducing symptoms of MG. This confirms that additional immune mechanisms are important in pathogenesis of this disease. Allogeneic transplantation may be a therapeutic option for patients with severe, refractory MG. However, little is known about the long-term efficacy of allogeneic transplantation for this disease, and long-term follow-up is warranted.

Widely varying TNF-α levels in patients with myasthenia gravis

Animal studies have indicated an important role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of myasthenia gravis (MG), and trials of monoclonal antibodies that block TNF-alpha have shown clinical improvement. However, before a TNF-alpha blocking agent is proposed for treatment of MG, whether serum TNF-alpha level correlates with the patient's condition should be confirmed. Therefore, we evaluated the relationship between the serum TNF-alpha level and clinical factors, including the quantitative MG score and the anti-acetylcholine receptor antibody level, in 33 MG patients. TNF-alpha levels ranged from 0.44 to 3.63 pg/mL and did not correlate with clinical factors. Overall, we found that serum TNF-alpha levels varied greatly among MG patients.

Postthymectomy Myasthenia Gravis: Relationship With Thymoma and Antiacetylcholine Receptor Antibody

Myasthenia gravis occasionally develops in a postthymectomy patient with no preoperative history of this disease. We retrospectively assessed the clinical course, history, and findings of myasthenia gravis, and examined the serum titers of antiacetylcholine receptor-binding antibody in patients who had undergone thymectomy. We enrolled 67 patients with thymoma and 11 with other thymic tumors, all of whom underwent thymectomy. Twelve thymoma patients had had myasthenia gravis preoperatively, and their serum titers were all positive for antiacetylcholine receptor-binding antibody. Thirteen of 55 patients (24%) who had had no preoperative myasthenia gravis, but none with other thymic tumors (p < 0.0001), had a similar positive reaction. Five of the 55 thymoma patients without preoperative myasthenia gravis presented with the disease 3 to 46 months after thymectomy. These 5 patients showed no significant clinical or pathologic features, and in only 1 did the tumor recur. However, they all, including 2 patients who had shown negative antiacetylcholine receptor-binding antibody titers preoperatively, showed the presence of antiacetylcholine receptor antibody after onset. No postoperative elevation of the antiacetylcholine receptor binding antibody titer was observed in any postthymectomy patient who had no myasthenia gravis. We found that patients in whom postthymectomy myasthenia gravis developed showed high titers of antiacetylcholine receptor-binding antibody at the onset of the myasthenia gravis. We suggest that a positive preoperative antiacetylcholine receptor antibody level may be a risk factor for postthymectomy myasthenia gravis.

Dropped Head Sign as the Only Symptom of Myasthenia Gravis

Neck extensor muscle weakness and the dropped head sign are associated with various neuromuscular disorders. However, these symptoms are comparatively rare in myasthenia gravis (MG). We report a MG case that presented with dropped head sign as the main symptom. A 55-year-old man developed subacute weakness of the neck extensor muscle and presented with dropped head. We established a diagnosis of MG based on the results of an edrophonium test and a voluntary single fiber electromyogram (vSFEMG), and a high serum antiacetylcholine receptor antibody level. This patient was treated with pyridostigmine and his neurological symptoms improved. There are reported cases of dropped head sign as the first symptom of MG, however, in those cases, other muscles showed weakness during the first few months after onset. In the present case, throughout the clinical course no other symptoms outside of dropped head sign were seen.

Thymolipoma associated with myasthenia gravis

A 51-year-old woman with a 3-year history of diplopia was admitted to our hospital. Repetitive stimulation of the right median nerve revealed decreasing hand muscle responses. Edrophonium chloride administration alleviated the symptoms. The serum antiacetylcholine receptor antibody level was 3.3 nmol/l; thus, myasthenia gravis was diagnosed. A chest roentgenogram revealed a left inferior mediastinal mass, and a chest computed tomographic scan revealed a fat density mass partly containing soft tissue areas in the left side of the anterior mediastinum. Median sternotomy and extended thymectomy were performed. The pathology examination of the tumor revealed mature adipose tissue including islands of thymic tissue containing Hassall's corpuscles, without germinal centers. The tumor was a thymolipoma of the anterior mediastinum. Her postoperative course was good, and she is doing well at 1 year postoperatively.

Myasthénie auto-immune et grossesse : évolution clinique, accouchement et post-partum

To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital. Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis. During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies. Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.

Autoimmune Myasthenia Gravis After Coronary Artery Bypass Surgery

Myasthenia gravis is the most common disorder of neuromuscular transmission and is a heterogeneous disorder that is generally autoimmune, which is caused by an auto-antibody to the nicotinic acetylcholine receptor. We present a rare case of myasthenia gravis that occurred 8 weeks after a coronary artery bypass grafting operation. A 64-year-old man with multivessel coronary artery disease underwent myocardial revascularization. Severe myasthenic symptoms began 8 weeks after the operation and emergent mechanical ventilation was needed because of myasthenic crises. The serum anti-acetylcholine receptor antibody level was high. The details of this unusual patient are discussed.

Myasthenia gravis patients with low plasma IL-6 and IFN-γ benefit from etanercept treatment

Steroid-dependent myasthenia gravis patients improved following treatment with etanercept (recombinant human TNF receptor:Fc) in a prospective pilot trial. While the plasma anti-acetylcholine receptor antibody levels remained unaffected, etanercept treatment increased plasma levels of C3, circulating immune complexes, IL-10 and IFN-γ. There was a direct correlation between plasma IL-6, TNF-α and IFN-γ levels and the post-treatment clinical scores of patients. Moreover, patients with lower pre-treatment plasma IL-6 and IFN-γ levels attained better clinical improvement following etanercept treatment.

Interleukin-2 Production by Peripheral Blood Mononuclear Cells from Patients with Myasthenia gravis

We examined interleukin-2 (IL-2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMs) from 75 untreated myasthenia gravis (MG) patients and 48 control patients. Patients with MG consisted of those with elevated PBM IL-2 production (>1,250 pg/ml; mean + 2SD of the controls) (n = 29, 39%) and those with normal PBM IL-2 production (<1,250 pg/ml) (n = 46, 61%). Significant characteristics of patients with elevated PBM IL-2 production included elevated serum levels of anti-acetylcholine receptor antibodies, severe generalized symptoms, thymic hyperplasia, and marked effects of thymectomy (p < 0.05). These findings suggest that elevated PBM IL-2 production can reflect functional abnormalities of T cells in some patients with MG, and that PBM IL-2 production should be considered as a candidate target of therapy.

Heterogeneous immunogenetic background in Japanese adults with myasthenia gravis

The aim of this study was to elucidate the roles of human leukocyte antigen (HLA) class II genes in disease susceptibility in Japanese adult patients with myasthenia gravis (MG). A number of studies have shown that MG is correlated with DR3 in Caucasians. In Japanese, infantile MG is associated with DR9, but the HLA class II alleles associated with adult MG remains unclear. HLA-DRB1 and DQB1 alleles were determined by genotyping in 75 Japanese adult patients with MG and in 115 race-matched healthy adults. No statistically significant difference was observed in the overall prevalences of DRB1 and DQB1 alleles between MG patients and healthy controls, even when the patients and controls were stratified on the basis of their gender. MG patients with DQB1*0604 were younger and those with DQB1*0402 were older at disease onset than those without ( P=0.03 and 0.008, respectively). Concomitant autoimmune thyroid disease was associated with DRB1*0803 ( P=0.0009, corrected P=0.04). In addition, anti-acetylcholine receptor antibody levels were significantly higher in patients with DQB1*0604 than in those without ( P=0.045). These findings indicate that immunogenetic backgrounds in Japanese adult MG patients are heterogeneous and are apparently different from those in Caucasian patients.