RESUMO
PURPOSE: Preoperative neutrophil count is reportedly associated with poor prognosis in cancer patients. This study aimed to investigate the clinical significance of pre-treatment peripheral blood cell counts in patients with thymic epithelial tumors (TETs). METHODS: A retrospective review of 71 patients with completely resected TETs [64 thymoma, 6 thymic carcinoma, and 1 thymic neuroendocrine tumor] between 2000 and 2018 was conducted. Associations between tumor recurrence and pre-treatment peripheral blood cell counts of leukocytes (WBC), neutrophils (Neut), lymphocytes (Lymph), monocytes (Mono), and platelets (Plt) were analyzed. Optimal cut-off points were selected using receiver operating characteristic curve analysis to predict tumor recurrence. RESULTS: High WBC (≥ 7000), Neut (≥ 4450), and Plt (≥ 226 × 103) counts had significantly poor relapse-free survival (RFS), but high Lymph (≥ 1950) and Mono (≥ 400) did not. High Neut had the strongest correlation with recurrence (area under curve, 0.800); we focused on the analysis between high-Neut and low-Neut groups. High Neut count significantly correlated with smoking history, pre-treatment C-reactive protein level, and advanced stage; high Neut count and aggressive histology tended to show correlations. RFS was significantly poorer in the high-Neut group than in the low-Neut group (p = 0.003), with 5-year RFS rates of 63.8% and 96.8%, respectively. High Neut count was a significant adverse predictor for RFS and cumulative incidence of recurrence (p = 0.005 and p < 0.001, respectively). The risk scoring system comprising high Neut count, advanced stage, and aggressive histology demonstrated better prognostic ability than any prognostic factors alone. CONCLUSIONS: High Neut count significantly correlated with TET recurrence, suggesting a negative prognostic effect of latent inflammation in TET patients.
Assuntos
Neoplasias Epiteliais e Glandulares , Neutrófilos , Neoplasias do Timo , Humanos , Contagem de Leucócitos , Linfócitos/patologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/patologia , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/patologia , Neutrófilos/patologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Timoma/sangue , Timoma/patologia , Neoplasias do Timo/sangue , Neoplasias do Timo/patologiaRESUMO
Tumor growth and its chemotherapeutic regimens manifest myelosuppression, which is one of the possible causes underlying the limited success of immunotherapeutic anticancer strategies. Hence, approaches are being designed to develop safer therapeutic regimens that may have minimal damaging action on the process of myelopoiesis. 3-Bromopyruvate (3-BP) is a highly potent antimetabolic agent displaying a broad spectrum antineoplastic activity. However, 3-BP has not been investigated for its effect on the process of myelopoiesis in a tumor-bearing host. Hence, in this investigation, we studied the myelopoietic effect of in vivo administration of 3-BP to a murine host bearing a progressively growing ascitic thymoma designated as Dalton's lymphoma (DL). 3-BP administration to the DL-bearing mice resulted in a myelopotentiating action, reflected by an elevated count of bone marrow cells (BMC) accompanied by augmented proliferative ability and a declined induction of apoptosis. The BMC of 3-BP-administered mice displayed enhanced responsiveness to macrophage colony-stimulating factor for colony-forming ability of myeloid lineage along with an enhanced differentiation of F4/80+ bone marrow-derived macrophages (BMDM). BMDM differentiated from the BMC of 3-BP-administered DL-bearing mice showed an augmented response to lipopolysaccharide and interferon-γ for activation, displaying an augmented tumor cytotoxicity, expression of cytokines, reactive oxygen species, nitric oxide, CD11c, TLR-4, and HSP70. These features are indicative of the differentiation of M1 subtype of macrophages. Thus, this study demonstrates the myelopotentiating action of 3-BP, indicating its hematopoietic safety and potential for reinforcing the differentiation of macrophages in a tumor-bearing host.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Piruvatos/uso terapêutico , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Animais , Ascite , Células da Medula Óssea , Diferenciação Celular , Proliferação de Células , Macrófagos , Camundongos Endogâmicos BALB C , Mielopoese/efeitos dos fármacos , Complexo Piruvato Desidrogenase , Timoma/sangue , Neoplasias do Timo/sangueRESUMO
BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.
Assuntos
Síndrome de Isaacs/complicações , Miastenia Gravis/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Adulto , Autoanticorpos/sangue , Eletromiografia , Feminino , Humanos , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Recidiva Local de Neoplasia , Netrina-1/imunologia , Estudos Retrospectivos , Timoma/sangue , Neoplasias do Timo/sangueRESUMO
PURPOSE: The preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with a poor prognosis for various cancers. We evaluated the prognostic role of the preoperative NLR in patients with thymoma. METHODS: We reviewed the medical records of 254 patients who underwent resection of thymic epithelial tumors at our institution. Patients were excluded if they had received steroid therapy, neoadjuvant therapy, or incomplete resection, or if they had thymic carcinoma or Good's syndrome, recurrence of thymoma, or missing data. The NLR was measured preoperatively, and outcomes of patients with a low (< 1.96) vs those with a high (≥ 1.96) NLR were compared statistically. RESULTS: Of 159 eligible patients, 59 (37.1%) had a high NLR and 100 (62.9%) had a low NLR. Overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS), disease-related survival (DRS), and the cumulative incidence of recurrence (CIR) differed significantly between the groups. Multivariate analyses revealed that a high NLR was independently associated with disease-related survival and a cumulative incidence of recurrence. A high NLR was also associated with a higher risk of recurrence of Masaoka stage I or II thymoma. CONCLUSIONS: An elevated preoperative NLR was associated with poor outcomes after thymoma resection. Thus, the NLR may be a useful biomarker of the postoperative prognosis of thymoma.
Assuntos
Biomarcadores Tumorais/sangue , Contagem de Leucócitos , Linfócitos , Neutrófilos , Timoma/diagnóstico , Timoma/cirurgia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Taxa de Sobrevida , Timoma/sangue , Timoma/mortalidade , Neoplasias do Timo/sangue , Neoplasias do Timo/mortalidade , Adulto JovemRESUMO
A 46-year-old man was referred to our hospital with a suspicion of pericardial cyst. Chest computed tomography (CT) revealed an anterior mediastinal tumor. He had no symptoms, but laboratory data showed positive titer to acetylcholine receptor antibody (Anti-AchR Ab). Under a clinical diagnosis of thymoma, extended thymectomy was performed. This case may represent subclinical myasthenia gravis, so we suggest extended thymectomy is crucial for thymoma with elevated level of Anti-AchR Ab without any symptoms.
Assuntos
Autoanticorpos/sangue , Miastenia Gravis , Receptores Colinérgicos/imunologia , Timoma/imunologia , Neoplasias do Timo/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Timectomia/métodos , Timoma/sangue , Timoma/cirurgia , Neoplasias do Timo/sangue , Neoplasias do Timo/cirurgiaRESUMO
OBJECTIVE: Oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases. Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, and its antioxidant status is still controversial. Our study aimed to investigate the correlation between the clinical characteristics of MG and the serum antioxidant status of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine. MATERIALS AND METHODS: We measured serum antioxidant molecule levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine in 380 individuals, including 166 MG and 214 healthy controls. RESULTS: We found that MG patients had significantly lower serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine than healthy controls, whether male or female. Moreover, it was also shown in our study that uric acid, albumin and creatinine levels in patients with MG were correlated with disease activity and classifications performed by the Myasthenia Gravis Foundation of America. CONCLUSION: Our findings demonstrated that serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine were reduced in patients with MG. This suggested an active oxidative process in MG patients who had low antioxidant status.
Assuntos
Bilirrubina/sangue , Creatinina/sangue , Miastenia Gravis/sangue , Albumina Sérica/metabolismo , Ácido Úrico/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/fisiopatologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/sangue , Timoma/sangue , Timoma/patologiaRESUMO
BACKGROUND: miR-15b is significantly and consistently downregulated in different clinical phenotypes of myasthenia gravis (MG). However, its role in pathogenesis of MG is still not clear. This study aimed to explore the function of miR-15b in MG. MATERIAL AND METHODS: Blood samples from early-onset MG, late-onset MG, thymoma patients, and healthy participants were collected. The expression pattern of IL-15 and miR-15b was identified by qRT-PCR and ELISA in patient serum and mouse tissue samples. The regulative role of miR-15b on IL-15 expression was verified in an experimental autoimmune myasthenia gravis (EAMG) mice model. RESULTS: qRT-PCR and ELISA showed that miR-15b expression was significantly lower and IL-15 expression was significantly higher in all EMG, LMG, and thymoma cases compared to healthy controls. Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice. Through searching in bioinformatics databases, we identified a highly conserved consequential pairing between IL-15 and miR-15b. Subsequent dual luciferase assay further verified this match. CONCLUSIONS: This study is the first to report the miR-15b-IL-15 axis can directly regulate IL15 expression, which helps to further explain the abnormal IL-15 expression in MG patients and the pathogenesis of MG.
Assuntos
Regulação da Expressão Gênica/fisiologia , Interleucina-15/metabolismo , MicroRNAs/sangue , Miastenia Gravis Autoimune Experimental/metabolismo , Miastenia Gravis/fisiopatologia , Animais , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Técnicas de Silenciamento de Genes , Humanos , Luciferases , Camundongos , MicroRNAs/genética , Miastenia Gravis/sangue , Reação em Cadeia da Polimerase em Tempo Real , Timoma/sangueRESUMO
A 73-year-old woman complained of right chest discomfort. Chest X-ray during the follow-up for rheumatoid arthritis showed a mediastinal tumor. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a 65-mm tumor in the right anterior mediastinum. A blood test showed high serum levels of CYFRA 21-1(29.8 ng/ml), white blood cells( WBC 10,800/µl), and C-reactive protein(CRP 16.1 mg/dl). Subsequently, inflammatory reactions improved, and the thymic tumor was resected. Histopathologically, the tumor was a type B2 thymoma with extensive coagulative necrosis. After resection, the serum CYFRA 21-1 level returned to the normal range.
Assuntos
Antígenos de Neoplasias/sangue , Queratina-19/sangue , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Idoso , Feminino , Humanos , Necrose , Timoma/sangue , Timoma/patologia , Neoplasias do Timo/sangue , Neoplasias do Timo/patologia , Tomografia Computadorizada por Raios XRESUMO
Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Eosinófilos/imunologia , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/imunologia , Timoma/imunologia , Neoplasias do Timo/imunologia , Animais , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Modelos Animais de Doenças , Eosinófilos/metabolismo , Feminino , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Incidência , Interleucina-5/efeitos adversos , Interleucina-5/imunologia , Interleucina-5/uso terapêutico , Contagem de Leucócitos , Masculino , Camundongos , Prognóstico , Medição de Risco , Timoma/sangue , Timoma/epidemiologia , Neoplasias do Timo/sangue , Neoplasias do Timo/epidemiologiaRESUMO
BACKGROUND: No useful tumor markers have been identified for the diagnosis of thymic carcinomas. Serum cytokeratin 19 fragment, measured using the CYFRA 21-1 immunoassay, is used as a tumor marker for squamous cell carcinomas in various malignant tumors. Here, we evaluated the value of CYFRA 21-1 in diagnosing thymic carcinoma. METHODS: We retrospectively reviewed 94 patients with pathological diagnoses of thymic carcinoma or thymoma (32 and 62 patients, respectively) who were referred to our departments between January 2000 and March 2019. Primary outcomes included tumor marker levels and their diagnostic accuracy. RESULTS: Patients with thymic carcinoma were significantly more likely to be male (thymic carcinoma, 68.8%; thymoma, 40.3%; p = 0.02), have an advanced TNM stage (p < 0.01), and a significantly higher CYFRA 21-1 level than those with thymoma (thymic carcinoma: median = 4.2 ng/ml; interquartile range [IQR] = 2.1-6.1 ng/ml vs. thymoma: median = 1.2 ng/ml; IQR = 0.9-1.7 ng/ml; p < 0.01). Receiver operating characteristic curves demonstrated that the area under the curve for CYFRA 21-1 to distinguish thymic carcinoma from thymoma was 0.86 (95% confidence interval [CI]: 0.74-0.93; cutoff = 2.7 ng/ml; sensitivity = 68.8%; specificity = 95.2%). Multivariable analysis demonstrated that CYFRA 21-1 (odds ratio = 25.6; 95% CI: 4.6-141.6; p < 0.01) was an independent predictor for thymic carcinoma after adjusting for TNM stage. CONCLUSIONS: Serum CYFRA 21-1 level may help in diagnosing thymic carcinoma.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Queratina-19/sangue , Timoma/diagnóstico , Neoplasias do Timo/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Timoma/sangue , Neoplasias do Timo/sangueRESUMO
BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated. RESULTS: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy. DISCUSSION: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.
Assuntos
Linfócitos B , Leucócitos Mononucleares , Linfopoese , Miastenia Gravis , Células-Tronco , Linfócitos T , Timoma , Neoplasias do Timo , Adolescente , Adulto , Idoso , Linfócitos B/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Miastenia Gravis/fisiopatologia , Células-Tronco/imunologia , Linfócitos T/imunologia , Timectomia , Timoma/sangue , Timoma/imunologia , Timoma/fisiopatologia , Neoplasias do Timo/sangue , Neoplasias do Timo/imunologia , Neoplasias do Timo/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Thymomas are the most common primary malignant tumors of anterior mediastinal. However, there are no specific laboratory indicator for the diagnosis the diagnosis of thymoma. The aim of this study was to screen out a tumor marker for diagnosis of thymoma by mRNA microarray analysis and confirmed it. METHODS: By mRNA microarray analysis of 31 thymomas and peritumoral thymic tissues, we found that the transcription level of neuronal pentraxin 1 (NPTX1) gene was up-regulated more than 4 times in thymomas. To further verify the above results, we detected the transcription and expression level of NPTX1 in 60 thymoma and 30 thymic cyst patients by quantitative Real-Time polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Furthermore, the diagnostic value of NPTX1 in thymoma by receiver operating characteristic curve (ROC) was analyzed. RESULTS: The transcription level of NPTX1 mRNA in thymoma tissues was significantly higher than that in the thymic tissues of control group [(2.88±1.02) vs (1.35±0.47), P<0.001); The expression level of NPTX1 in thymoma tissues was significantly higher than that in the thymic tissues of control group (2 vs 1, P<0.001); The preoperative serum level of NPTX1 protein in thymoma patients were significantly higher than that in the thymic cyst patients of control group [(1,018.29±209.38) pg/mL vs (759.95±66.02) pg/mL, P<0.001]; At the threshold of 842.22 pg/mL, sensitivity and specificity of NPTX1 as a serologic marker were 85.00% and 93.33%, respectively for thymoma. ROC showed that the area the under curve (AUC) of NPTX1 was 0.902. CONCLUSIONS: NPTX1 was highly expressed in thymoma patients, and had diagnostic value for thymoma.
Assuntos
Proteína C-Reativa/genética , Neoplasias Pulmonares/diagnóstico , Proteínas do Tecido Nervoso/genética , Timoma/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/sangue , Curva ROC , Timoma/sangue , Timoma/genética , Timoma/patologia , Adulto JovemRESUMO
We report a case of thymoma-associated autoimmune encephalitis with positive Titin antibodies. The patient had cognitive dysfunction, psychiatric symptoms and symptomatic epilepsy. PET-CT indicated space-occupied lesion at the thoracic entrance. The patient was diagnosed with paraneoplastic autoimmune encephalitis. After immunotherapy, his condition improved and underwent thymectomy. Pathology revealed type A thymoma. The patient recurred 10 days after the operation. Thymoma is associated with AE. And Titin antibodies may be involved in the extensive immune response to antigens which the patient's thymoma ectopically expressed. This case reflects the complexity of the immune relationship among autoimmune encephalitis, Titin antibodises and thymoma. Titin antibody may have a certain guiding significance for the treatment and prognosis of autoimmune encephalitis.
Assuntos
Conectina/sangue , Encefalite/sangue , Doença de Hashimoto/sangue , Timoma/sangue , Neoplasias do Timo/sangue , Adulto , Encefalite/complicações , Encefalite/diagnóstico por imagem , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico por imagem , Humanos , Masculino , Timoma/complicações , Timoma/diagnóstico por imagem , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico por imagemAssuntos
Leucócitos/patologia , Neutropenia/diagnóstico , Timoma/complicações , Neoplasias do Timo/complicações , Idoso , Exame de Medula Óssea , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Humanos , Contagem de Leucócitos , Masculino , Neoplasias do Mediastino/diagnóstico , Neutropenia/complicações , Timoma/sangue , Neoplasias do Timo/sangueRESUMO
Antititin antibody occurs in the serum of myasthenia gravis (MG) patients with thymoma (MGT), and is a diagnostic marker for the disease. The mechanism that triggers MGT development is, however, unclear. This study evaluated the role of the main immunogenic region (MIR) of titin in MGT pathogenesis. Titin MIR antiserum (antibody titre 1:16) was obtained and an in situ immunohistochemical study of thymomatous tissue samples was performed. Strong immunostaining for titin MIR was observed on epithelial cell membranes in MGT patients, and the degree of immunostaining was directly proportional to the number of epithelial cells in thymomatous tissue. Serum antititin antibody levels were closely related to titin MIR levels in thymoma cells; however, titin MIR levels did not appear to be related to MG severity. Antititin antibody may be a good surrogate marker for thymoma but is probably not involved in the pathogenesis of MGT.
Assuntos
Proteínas Musculares/imunologia , Miastenia Gravis/complicações , Miastenia Gravis/metabolismo , Proteínas Quinases/imunologia , Timoma/complicações , Timoma/metabolismo , Timo/metabolismo , Adolescente , Adulto , Idoso , Anticorpos/sangue , Criança , Pré-Escolar , Conectina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/química , Miastenia Gravis/sangue , Miastenia Gravis/patologia , Proteínas Quinases/química , Estrutura Terciária de Proteína , Timoma/sangue , Timoma/patologia , Timo/patologia , Adulto JovemRESUMO
Thymoma is the most common tumor of the anterior mediastinum. Routine imaging methods such as computed tomography or magnetic resonance imaging often lead to misdiagnosis between thymoma and other thymic abnormalities. Therefore, urgently needed is to develop a new diagnostic strategy. Here we identify interleukin-8 (IL-8) as a biomarker for auxiliary diagnosis of thymoma. We find that IL-8 levels in naïve T cells are markedly elevated in patients with thymoma compared to those with other thymic tumors. IL-8 levels in naive T cells are significantly decreased after surgical resection in thymoma patients, and rise again when thymoma recurs. A receiver operating characteristic curve analysis shows that IL-8 evaluation performs well in thymoma identification, with high specificities and sensitivities. We also observe significant clinical relevance between IL-8 levels in naïve T cells and clinicopathological features. In conclusion, our study suggests that IL-8 is a biomarker for thymoma identification and recurrence surveillance.
Assuntos
Interleucina-8/sangue , Recidiva Local de Neoplasia/sangue , Timoma/sangue , Neoplasias do Timo/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Interleucina-8/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Timoma/genética , Timoma/patologia , Neoplasias do Timo/genética , Neoplasias do Timo/patologia , Adulto JovemRESUMO
OBJECTIVE: To improve myasthenia gravis (MG) autoantibody testing. METHODS: MG serologic tests with confirmatory or refuting clinical-electrodiagnostic (EDX) testing and cancer evaluations were reviewed over 4 years (2012-2015). All patients had acetylcholine receptor-binding (AChR-Bi), modulating (AChR-Mo), and striational (STR) autoantibody testing, and negatives reflexed to muscle-specific kinase (MuSK). Thymoma and cancer occurrences were correlated with STR and reflexed glutamic acid decarboxylase 65 (GAD65), ganglionic acetylcholine receptor (α3), collapsin response mediating protein-5, and voltage-gated potassium channel complex autoantibodies. RESULTS: Of 433 samples tested, 133 (31%) met clinical-EDX criteria for MG. Best sensitivity (90%) occurred at AChR-Bi >0.02 nmol/L, leaving 14 negative (6 ocular MG, 7 generalized MG, 1 MuSK MG) with specificity 90% (31 false-positives). Using AChR-Mo antibodies (>20% loss), specificity was better (92%, 24 false-positives), but sensitivity dropped (85%). Specificity improved (95%) by testing AChR-Mo when AChR-Bi are positive, resulting in 45% reduction of false-positives (31-17), maintaining AChR-Bi 90% sensitivity. Cutoff values recommended by area under the curve analysis did not outperform this approach. AChR-Bi and AChR-Mo values were significantly higher in true-positives. CT evaluations in 121 MG samples revealed 16 thymomas. Historical or subsequent cancers occurred in 22. STR and reflexed autoantibodies were not more common in MG with thymoma or other cancers. Full-body CT (n = 34) was performed in those with STR and reflex autoantibody positivity, but without additional cancers found. CONCLUSION: Accuracy of MG serologic testing is improved by reflexing AChR-Bi-positive cases to AChR-Mo. STR and other reflexed cancer evaluation autoantibodies did not provide value beyond standard CT chest imaging at the time of MG diagnosis. Diagnostic certainty is informed by AChR-Bi and AChR-Mo with higher values increasing specificity.
Assuntos
Autoanticorpos/sangue , Testes Imunológicos/normas , Miastenia Gravis/diagnóstico , Timoma/diagnóstico , Neoplasias do Timo/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Eletrodiagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Timoma/sangue , Timoma/imunologia , Neoplasias do Timo/sangue , Neoplasias do Timo/imunologia , Adulto JovemRESUMO
Extended thymectomy is employed for patients with myasthenia gravis (MG) and/or thymoma with elevated serum antiacetylcholine receptor antibody (AchR) titers. However, MG symptoms occasionally worsen in post-thymectomy patients. We explored the risk factors for exacerbation of MG symptoms after surgical therapy for patients with MG and/or thymoma with an elevated AchR titer. We retrospectively analyzed 90 patients suffering from MG and/or thymoma with an elevated AchR titer who underwent thymectomy in our institute. Patients were classified into Improved, Unchanged, and Exacerbated groups by assessing their postoperative myasthenic symptoms, amount of medication, and incidence of myasthenic crisis. Risk factors for postoperative exacerbation of myasthenic symptoms were assessed by comparing the Exacerbated with the Improved and Unchanged groups. Of the 90 patients, 29 were classified into the Improved group, 47 into the Unchanged group, and 14 into the Exacerbated group. The presence of thymoma and Masaoka stage were significantly different between the Exacerbated and Improved/Unchanged groups. Although preoperative AchR titers did not significantly differ among the groups, the perioperative AchR titers in the Exacerbated group were significantly higher than those in the other groups (Pâ¯=â¯0.003). A multiple logistic regression analysis with stepwise forward selection showed that advanced-stage thymoma was a risk factor for postoperative exacerbation of myasthenic symptoms (Pâ¯=â¯0.007). Patients with advanced-stage thymoma have a relative risk for exacerbation of myasthenic symptoms after surgical therapy.
Assuntos
Miastenia Gravis/cirurgia , Timectomia/efeitos adversos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Idoso , Autoanticorpos/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/diagnóstico , Estadiamento de Neoplasias , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Timoma/sangue , Timoma/diagnóstico , Neoplasias do Timo/sangue , Neoplasias do Timo/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to analyze the impact of thymectomy on kinetics of the immune reconstitution in thymoma patients. Nine consecutive patients with completely resected thymoma were enrolled. Immunophenotype analysis (total lymphocytes, CD3, CD4, CD8, CD19, NK subsets) and detection of autoantibodies at 6, 12, 18, and 24 months after thymectomy were planned. A prolonged inversion of CD4/CD8 ratio was present, due to a diminished number of CD4+ cells; CD8+ cell numbers remaining constantly normal at different time points; CD19+ cells remained for a long time understatement, achieving almost normal levels at 24 months; and NK cells always showed a normal amount. Autoantibodies against the muscle acetylcholine receptor were detected in four patients (44.4%) at the time of diagnosis, while antinuclear antibody were detected in eight patients (88.8%) at different time points during postthymectomy. A high incidence of multiple primary neoplasms was observed (66.6% of cases). Our study showed that cellular and humoral immune alterations are a common sequelae of postthymectomy. Further studies, a longer surveillance and a cooperative approach, due to the rarity of the disease, are necessary to define eventual implications of immune alterations on patient's outcome.
Assuntos
Timectomia , Timoma , Neoplasias do Timo , Idoso , Antígenos CD/imunologia , Autoanticorpos/imunologia , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Timoma/sangue , Timoma/imunologia , Timoma/cirurgia , Neoplasias do Timo/sangue , Neoplasias do Timo/imunologia , Neoplasias do Timo/cirurgiaRESUMO
BACKGROUND: Immunodeficiency with a thymoma (Good's syndrome) is a rare condition occurring in patients with adult-onset hypogammaglobulinaemia. CLINICAL REPORT: We describe the case of a 38-yr-old woman with an upper mediastinal mass and inflammatory infiltrations in the lungs. After thymectomy, the patient's condition did not improve. The HRCT scan showed bronchiectasies with parenchymal opacities. As pulmonary infection persisted despite wide spectrum antibiotic therapy, additional tests were performed to diagnose an immunodeficiency. Serum immunoglobulin levels were very low. T cell response to mitogens was normal, but to Staphylococcus aureus Cowan I was impaired. Immunophenotyping of peripheral blood and bone marrow aspirate showed a very low number of B-cell at all the stages of development (CD10+CD19+, CD5+CD20). In peripheral blood 2.5% of CD19+ lymphocytes were found. On the basis of clinical history and immunological analysis, Good's syndrome was recognized. Treatment with intravenous gammaglobulin and antibiotics improved the patient's performance. CONCLUSION: Measurement of serum immunoglobulin concentration is recommended for all patients suspected of thymoma.