Association between peripheral plasmablasts and postoperative exacerbation in patients with thymoma‐associated myasthenia gravis
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Abstract Objective Thymoma‐associated myasthenia gravis ( TAMG ) is a type of myasthenia gravis (MG) that has a higher likelihood of worsening in comparison with non‐ TAMG , and MG symptoms often worsen after thymectomy. We measured peripheral T/B lymphocyte subsets before and after thymectomy in TAMG patients , and investigated the relationships with the occurrence of postoperative exacerbation of MG symptoms. Methods Participants were 10 TAMG patients, 40 healthy controls and five other surgical control patients. Peripheral lymphocyte subsets were measured using FACS ‐Canto flow cytometry before, and 1, 7, and 28 days after thymectomy in the TAMG , and before and 7 days after thymectomy in the other surgical control patients. Results Natural killer cells modestly decreased, and plasmablasts increased significantly ( P = 0.005) after 7 days postoperatively in comparison with preoperative values. Conversely, no obvious changes were observed in plasmablasts or natural killer cells in T/B lymphocyte subsets. From evaluation of postoperative clinical course and plasmablasts, exacerbation of MG symptoms was observed between 2 and 3 weeks after thymectomy in five of 10 patients (50%) of TAMG . In these five patients, plasmablasts markedly increased after thymectomy in three patients, among whom two patients had originally shown high plasmablast levels before thymectomy. There were also two patients who exacerbated without changes in plasmablast levels. Conclusions In patients with exacerbation of neurological symptoms after thymectomy for TAMG , the plasmablast levels were originally high and/or became high postoperatively. Thus, elevated plasmablast levels could potentially be predictive of postoperative exacerbation of MG .Keywords:
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Myasthenia gravis (MG) is an autoimmune disease affecting nicotinic acetylcholine receptors. The clinical improvement that follows thymectomy in some myasthenic patients implicates thymic factors as well in the pathogenesis of MG. We have studied circulating immunoregulatory T cell subsets before and after thymectomy in 11 adult patients with MG. Six patients had thymic hyperplasia and five patients had atrophic thymus at the time of thymectomy. Before thymectomy, patients who subsequently were shown to have an atrophic thymus, had lower lymphocyte counts than either patients later shown to have a hyperplastic thymus (1315 +/- 143 lymphocytes/mm3 vs. 2434 +/- 350 lymphocytes/mm3, p less than 0.01), or age-matched controls (1315 +/- 143 lymphocytes/mm3 vs. 2636 +/- 589 lymphocytes/mm3, p less than 0.02). Moreover, after thymectomy, in MG patients with an atrophic thymus, there was a significant rise in lymphocyte count (from 1315 +/- 143 lymphocytes/mm3 to 2279 +/- 292 lymphocytes/mm3, p less than 0.02) beginning 3 days postthymectomy and persisting for at least 6 weeks thereafter. In comparison, patients with a hyperplastic thymus showed no change in circulating lymphocyte counts (p greater than 0.1). Enumeration of lymphocyte subsets in MG patients with an atrophic thymus demonstrated normal B cell numbers before and after thymectomy (p greater than 0.1), whereas, T cells were significantly decreased before thymectomy compared with age-matched normal subjects (859 +/- 82 T cells/mm3 vs. 2215 +/- 545 T cells/mm3, p less than 0.05), and rose to near normal levels after thymectomy (1796 +/- 294 T cells/mm3, p less than 0.02 compared with prethymectomy levels). Using monoclonal anti-T cell antibodies 3A1, OKT4, and OKT8, we found that, before thymectomy in the atrophic thymus group, 3A 1+ T cells were significantly depressed compared with postthymectomy levels (620 +/- 173 cells/mm3 vs. 1627 +/- 331 cells/mm3, p less than 0.02) as were OKT4+ cells 436 +/- 88 cells/mm3 vs. 1112 +/- 63 cells/mm3, p less than 0.001), In contrast, no significant change was seen after thymectomy in the OKT8+ cell subset (p greater than 0.1). MG patients with an atrophic thymus had decreased plasma cortisol levels postthymectomy compared with prethymectomy levels, whereas thymectomy in MG patients with a hyperplastic thymus effected no change in plasma cortisol levels. These data demonstrate in MG patients with an atrophic thymus that thymectomy has an effect on the number of circulating T cells, and in particular, on those T cells expressing antigens 3A1 and OKT4. This effect may in part be mediated by changes in plasma adrenal corticosteroid levels after thymectomy or may be due to a factor produced by atrophic thymuses in MG.
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Introduction: Myasthenia gravis is an antibody-mediated autoimmune disease. Approximately 10-15% of patients present with a thymoma, the presence of which is associated with greater severity of symptoms, myasthenic crisis, and irresponsiveness to front-line therapy. A thymectomy is recommended in young patients with generalized myasthenia gravis and in all patients presenting with thymoma. Clinical case: The patient was a 43-year-old woman, who first showed symptoms of myasthenic crisis in 2005 and presented with invasive thymoma managed with thymectomy and radiotherapy. In the subsequent three years, the patient presented with severe symptoms and two myasthenic crises that required mechanical ventilation and immunoglobulin treatment. Contrast chest computed tomography examinations showed no recurrence. Between 2009 and 2012, the patient experienced decreased symptom severity. In 2013, the patient presented with an exacerbation of symptoms; a contrast chest magnetic resonance scan showed a lesion in the anterior mediastinum, previously observed in 2011, suggestive of residual tissue as opposed to fibrosis. Regular management was started with immunoglobulins; a positron emission tomography scan was inconclusive, requiring a new resection, which showed no evidence of tumor recurrence. Conclusions: Patients with myasthenia gravis and those with myasthenia-related thymoma both share thymectomy as an element of treatment. However, following the procedure, exacerbation or reappearance of symptoms does not necessarily represent new alterations in the thymus.
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OBJECTIVE. The authors evaluated the role of antibodies to striated muscle and acetylcholine receptors in diagnostics of myasthenia gravis and thymoma, as well as outcomes of thymectomy and prognosis of myasthenia course. MATERIAL AND METHODS. The study investigated correlations of antibody content to striated muscles and acetylcholine receptors from the presence and size of thymoma, myasthenia in 157 patients with various pathologies of the thymus. The dynamics of antibody concentrations was followed up after thymectomy. RESULTS. Antibody titer to striated muscle depended on the presence and size of thymoma, severity of myasthenia and changed after thymectomy. Concentration of antibodies was associated with the presence of thymoma and it didn’t change after surgical treatment. Thymoma wasn’t revealed in patients who were seronegative to both antibodies. CONCLUSIONS. Seropositivity according to one of antibody could indicate the presence of thymoma, but its absence to both antibodies allowed doctors to eliminate this diagnosis. Antibodies to acetylcholine receptors are important markers of myasthenia. Monitoring of antibody titer dynamics to striated muscles after thymectomy could be useful for assessment of response to surgical treatment and prognosis of course of myasthenia.
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Introduction: Myasthenia gravis is an antibody-mediated autoimmune disease. Approximately 10-15% of patients present with a thymoma, the presence of which is associated with greater severity of symptoms, myasthenic crisis, and irresponsiveness to front-line therapy. A thymectomy is recommended in young patients with generalized myasthenia gravis and in all patients presenting with thymoma.Clinical case: The patient was a 43-year-old woman, who first showed symptoms of myasthenic crisis in 2005 and presented with invasive thymoma managed with thymectomy and radiotherapy. In the subsequent three years, the patient presented with severe symptoms and two myasthenic crises that required mechanical ventilation and immunoglobulin treatment. Contrast chest computed tomography examinations showed no recurrence. Between 2009 and 2012, the patient experienced decreased symptom severity. In 2013, the patient presented with an exacerbation of symptoms; a contrast chest magnetic resonance scan showed a lesion in the anterior mediastinum, previously observed in 2011, suggestive of residual tissue as opposed to fibrosis. Regular management was started with immunoglobulins; a positron emission tomography scan was inconclusive, requiring a new resection, which showed no evidence of tumor recurrence.Conclusions: Patients with myasthenia gravis and those with myasthenia-related thymoma both share thymectomy as an element of treatment. However, following the procedure, exacerbation or reappearance of symptoms does not necessarily represent new alterations in the thymus.
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症例は胸腺腫を合併した重症筋無力症(myasthenia gravis,以下MGと略記)の62歳女性である.嚥下障害が著明で,副腎皮質ステロイド,免疫グロブリン大量静注療法(Intravenous immune globulin,以下IVIGと略記),免疫吸着療法(immunoadsorption plasmapheresis,以下IAPPと略記),免疫抑制剤により一旦改善したが,拡大胸腺摘出術後3週間で嚥下障害が再増悪した.IVIG,IAPPを行うも症状が残存し難渋したが,エクリズマブ開始後に症状は完全に消失し,MGの術後増悪に対して抗補体療法の有効性が示唆された.
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Myasthenia gravis is a disease that affects the neuromuscular junction causing abnormal weakness,
fatigue, and muscle decay. Loss or dysfunction of acetylcholine receptors occurs mostly due to the
presence of antibodies to nicotinic acetylcholine receptors (NAChR). The thymus and thymoma
have a special role in the pathophysiology of myasthenia gravis due to the role of the thymus in
the maturation and distribution of lymphocytes where cross-reactivity and consequent
autoimmunity to NAChR can occur. The most commonly used diagnostic method for myasthenia
gravis is the measurement of antibody levels to NAChR which is a highly specific test for the
diagnosis of myasthenia gravis. CT is the method of choice in the diagnosis of thymoma. Due to
the importance of the thymus in the pathophysiology of myasthenia gravis the disease can be
treated surgically, by removing the thymus. If there is thymoma present, to plan the operation,
Masaoka and TNM classification are used. Methods that can be used to remove the thymus /
thymoma are transsternal thymectomy, transcervical thymectomy, video-assisted thoracoscopic
surgery (VATS) and robotic surgery. Some of the factors influencing the prognosis after
thymectomy are age and sex, presence of thymoma, surgical technique, extent of resection and
severity and duration of symptoms of myasthenia gravis. New methods of thymectomy are
minimally invasive and with rapid recovery, and most patients show remission of the disease after
removal of thymus.
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