Gamma delta T lymphocytes in human tuberculosis.

The manifestations of tuberculous infection reflect the immune response to infection. Most healthy tuberculin reactors develop protective immunity; tuberculous pleuritis reflects a resistant response manifest by mild disease, whereas advanced pulmonary and miliary tuberculosis reflect ineffective immunity. The role of gamma delta T cells was assessed in tuberculous infection by evaluating expansion of these cells from blood mononuclear cells after stimulation with Mycobacterium tuberculosis. After culture in vitro, the percentages of gamma delta+ cells were significantly greater in patients with protective and resistant immunity (tuberculin reactors, 25% +/- 4%; tuberculous pleuritis, 30% +/- 7%) than in those with ineffective immunity (advanced pulmonary tuberculosis, 9% +/- 3%; miliary tuberculosis, 2% +/- 1%). In leprosy, expansion of gamma delta+ cells was greater in immunologically resistant tuberculoid patients (32% +/- 4%) than in Mycobacterium leprae-unresponsive lepromatous patients (9% +/- 2%). M. tuberculosis-reactive gamma delta T cell lines produced interferon-gamma, granulocyte-macrophage colony-stimulating factor, interleukin-3, and tumor necrosis factor-alpha, cytokines that activate macrophages and may contribute to mycobacterial elimination. These findings suggest that gamma delta T cells contribute to immune resistance against M. tuberculosis.     

Tuberculous pleurisy as a manifestation of primary and reactivation disease in a region with a high prevalence of tuberculosis.

SETTING: A teaching hospital in Malaysia. OBJECTIVE: To review the demographic and clinical features of patients with pleural tuberculosis (TB). DESIGN: Retrospective chart and chest radiograph review. RESULTS: The chest radiograph of 54 (61.4%) of a total of 88 patients with pleural TB did not show any lung infiltrate (considered a manifestation of primary TB), while that of 32 (36.3%) patients showed infiltrates in the upper lobes or superior segment of the lower lobes, or the presence of parenchymal scarring in the upper lobes (typical of reactivation TB). Additionally, the chest radiograph of two (2.3%) patients showed miliary mottling (also classified as having primary TB). The mean age of patients with primary versus reactivation tuberculous pleurisy was 36.3 (+/-14.8) years and 44.6 (+/-19.3) years, respectively (P = 0.041). The median duration of symptoms before presentation was 14 days and 60 days in patients with primary and reactivation disease, respectively (P = 0.001). CONCLUSION: In Malaysia, where the prevalence of TB is high, tuberculous pleurisy is more commonly a manifestation of primary rather than reactivation disease. Patients with primary TB pleurisy are younger and have a shorter duration of symptoms than those with reactivation TB pleurisy.     

Update on tuberculous pleural effusion

The possibility of tuberculous pleuritis should be considered in every patient with an undiagnosed pleural effusion, for if this diagnosis is not made the patient will recover only to have a high likelihood of subsequently developing pulmonary or extrapulmonary tuberculosis Between 3% and 25% of patients with tuberculosis will have tuberculous pleuritis. The incidence of pleural tuberculosis is higher in patients who are HIV positive. Tuberculous pleuritis usually presents as an acute illness with fever, cough and pleuritic chest pain. The pleural fluid is an exudate that usually has predominantly lymphocytes. Pleural fluid cultures are positive for Mycobacterium tuberculosis in less than 40% and smears are virtually always negative. The easiest way to establish the diagnosis of tuberculous pleuritis in a patient with a lymphocytic pleural effusion is to generally demonstrate a pleural fluid adenosine deaminase level above 40 U/L. Lymphocytic exudates not due to tuberculosis almost always have adenosine deaminase levels below 40 U/L. Elevated pleural fluid levels of γ‐interferon also are virtually diagnostic of tuberculous pleuritis in patients with lymphocytic exudates. In questionable cases the diagnosis can be established by demonstrating granulomas or organisms on tissue specimens obtained via needle biopsy of the pleura or thoracoscopy. The chemotherapy for tuberculous pleuritis is the same as that for pulmonary tuberculosis.     

The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis

STUDY OBJECTIVE: To examine the prevalence and characteristics of parenchymal tuberculous pleuritis in adult patients. DESIGN: Prospective cohort study. SETTING: Three hospitals affiliated with Seoul National University in South Korea. PATIENTS: All patients > 15 years old with a diagnosis of tuberculous pleuritis were enrolled prospectively between January 1, 2004, and October 31, 2004. INTERVENTIONS: Diagnostic thoracocentesis and CT of the chest were done for each patient. Acid-fast bacilli (AFB) smears and cultures for Mycobacterium tuberculosis were requested if patients produced any sputum. A board-certified radiologist reviewed the chest radiographs for the presence and characteristics of any lesions. MEASUREMENTS AND RESULTS: One hundred six patients with tuberculous pleuritis were enrolled (median age, 53 years; range 16 to 89 years). Among them, 33 patients (31%) had sputum or bronchial washing findings positive for AFB smears or for M tuberculosis by culture. Lung parenchymal lesions were observed in 91 of the patients (86%) using chest CT; 39 patients (37%) with parenchymal lesions had radiographic characteristics of active pulmonary tuberculosis. In total, 62 patients (59%) had bacteriologically or radiographically active pulmonary tuberculosis. In addition, 78 patients (74%) had features of reactivated pulmonary tuberculosis. CONCLUSIONS: Lung parenchymal lesions were more common in this series of patients with tuberculous pleuritis than has been reported in previous studies. The patients mostly had radiographic features of reactivated, rather than primary, tuberculosis.     

Der tuberkulöse Pleuraerguss

Approximately one third of the world’s population is infected with Mycobacterium tuberculosis and among communicable diseases tuberculosis is the second leading cause of death. The most common type of tuberculosis is pulmonary tuberculosis. Among the extrapulmonary manifestations, tuberculous pleuritis ranks second only after lymphatic tuberculosis. Tuberculous pleuritis is most commonly a disease with acute onset which is self-limiting in the majority of cases. A large proportion of patients though develop some form of active tuberculosis after a latency period. Therefore the correct diagnosis and the initiation of treatment are of the utmost importance. The easiest way to establish the diagnosis of tuberculous pleuritis is to demonstrate an elevated ADA (adenosine deaminase) in a lymphocytic effusion. Should pleural fluid analysis be nondiagnostic, the diagnosis of tuberculous pleuritis can be established with percutaneous closed needle biopsy in over 80% of cases. All patients with an undiagnosed pleural effusion after closed needle biopsy require thoracoscopy with selected biopsies taken under direct vision. The diagnostic yield of thoracoscopy is close to 100% in tuberculous pleuritis.     

Tuberculous pleural effusions

While a number of recent reports have documented the changing clinical and radiographic spectrum of parenchymal tuberculosis, relatively little attention has been paid to changes in the patterns of pleural tuberculosis. We therefore reviewed the clinical, laboratory, and radiographic characteristics of 26 adult patients with tuberculous pleural effusions. We found that pleural tuberculosis has become a disease of older adults (median age, 56 years) and that 19 percent (5/26) of the cases were due to postprimary (reactivation) disease. This shift in age led to problems in diagnosis, since many of these older patients had underlying or coexisting disease that could have caused a pleural effusion. Both specimens of pleural fluid and pleural biopsy were useful in establishing the diagnosis. Examination of sputum was less helpful. All patients who were not anergic had positive cutaneous reactions to first-strength purified protein derivative of tuberculin. Lymphocytosis of the pleural fluid was not a uniform finding; only 62 percent of our patients had greater than 50 percent lymphocytes on their initial examinations of pleural fluid, and four patients had greater than 90 percent polymorphonuclear cells. All of the effusions were exudates, and four had glucose levels in the pleural fluid that were less than 30 mg/dl. Pleural tuberculosis is an important diagnostic consideration in adult or elderly patients with exudative pleural effusions.     

Tuberculous pleural effusion and tuberculous empyema

Tuberculous pleuritis has increased worldwide, especially in developing countries, as a consequence of human immunodeficiency virus co-infection. Tuberculous pleuritis is a delayed hypersensitivity reaction against mycobacterial antigens in the pleural space. Mycobacteria are detected in less than 50% of pleural samples, but the characteristic pleural involvement, granulomas with or without caseous necrosis, is evident in 56 to 80% of cases from samples obtained by percutaneous pleural biopsy. Of several pleural fluid parameters studied, adenosine deaminase and interferon gamma (IFN-gamma) have the best diagnostic yield, while polymerase chain reaction remains a promising test. Treatment of patients with tuberculous pleuritis is discussed. Tuberculous empyema is a rare form of tuberculous pleuritis. It consists of a purulent infection of the pleural cavity with detectable bacilli in pleural fluid. Diagnosis is easily established clinically and bacteriologically. Treatment is to adequately drain the pleural space and achieve lung reexpansion, in conjunction with antituberculous chemotherapy. The efficacy of different surgical techniques is discussed.     

Lymphocyte proliferation and gamma-interferon production after "in vitro" stimulation with PPD. Differences between tuberculous and nontuberculous pleurisy in patients with positive tuberculin skin test

T-lymphocytes previously sensitized by an antigen undergo blastic transformation and produce IFN tau when stimulated by the same antigen. We studied the lymphoblastic response to PPD and IFN tau production in pleural fluid and peripheral blood of 41 patients (15 with tuberculous pleural effusion, 13 with nontuberculous pleurisy and positive tuberculin skin test, and 13 with tuberculin-negative nontuberculous pleurisy). In tuberculous pleuritis, pleural lymphocyte blastic response and IFN tau production were higher than those of peripheral lymphocytes, whereas in tuberculin-positive nontuberculous patients, peripheral lymphocyte response and IFN tau production were higher than those of pleural lymphocytes. Tuberculous pleural fluid lymphocytes underwent greater blastic transformation and produced more IFN tau than pleural lymphocytes of tuberculin-positive nontuberculous patients, whereas the opposite occurred in peripheral lymphocytes. In tuberculin-negative nontuberculous patients, there was no lymphoblastic response in either the pleural fluid or peripheral blood. These results concur with the concept of immunologic compartmentalization. In tuberculous pleuritis, there would be clonal expansion of PPD-responding T-lymphocytes in the pleural compartment. This expansion of PPD-specific lymphocytes would not occur in nontuberculous pleuritis, but lymphocytes sensitized to other antigens would accumulate in the pleural compartment.     

胸水和血清ADA、TB-Ab-IgG联合检测对结核性胸膜炎的诊断探讨

目的 探讨胸水/血清腺苷脱氨酶(ADA)、结核抗体(TB-Ab-IgG)联合检测对结核性胸膜炎的诊断价值.方法 采用斑点金免疫渗滤试验(DIGFA)和酶连续监测法对234例胸腔积液进行胸水/血清ADA和TB-Ab-IgG检测结果进行分析.结果 结核性胸膜炎患者174例其胸水、血清中TB-Ab-IgG的阳性率分别为62.0%和70.1%,特异性分别为93.1%(56/60)和86.6%(52/60).ADA活性在结核性和癌性胸腔积液中分别为(59.58±29.85)U/L和(15.31±7.36)U/L(P<0.01).以P-ADA>40 U/L做为诊断结核的临界值,其敏感性为79.3%,特异性为86.4%;以P-ADA/S-ADA>1为临界值,其敏感性为97.7%,特异性为95.5%.结论 胸水和血清ADA、TB-Ab-IgG联合检测在结核性胸膜炎与非结核性胸膜炎上具有诊断与鉴别诊断价值.     

The usefulness of pleural biopsy in benign or malignant pleurisy

Retrospective studies of pleural biopsy, cytology and ADA in pleural effusion were performed in 116 patients with pleural effusion between 1980 and 1988. Pleural malignant disease was diagnosed in 25 patients (75.8%) by cytology, in 19 patients (57.6%) by pleural biopsy. Thus, cytology should be performed first in patients with pleurisy. Both of cytologic study and CEA in pleural effusion were negative in 3 cases of squamous cell carcinoma. Tuberculous pleuritis was diagnosed in 24 patients (50.0%) by pleural biopsy, in 5 patients (10.4%) by isolation of Mycobacterium tuberculosis. Both pleural biopsy and adenosine deaminase activity (ADA) were examined in 19 cases of tuberculous pleuritis and ADA was elevated in 16 patients (84.2%). These data suggested that pleural biopsy was useful for diagnosis of pleuritis and the combination of cytology, tumor markers and ADA with biopsy improved diagnostic rates of pleuritis.     

The use of adenosine deaminase and adenosine deaminase isoenzymes in the diagnosis of tuberculous pleuritis

The bacillary population described in tuberculous pleuritis is small, and its most likely pathogenetic mechanism is essentially immunologic. This explains why, until now, the diagnostic identification of tuberculous pleuritis (TP) has been based on the presence of granulomas in pleural biopsy. Correcting this diagnostic deficiency through other parameters related to the specific pathogenetic mechanism has been widely studied. The determination of the levels of adenosine deaminase (ADA) in pleural fluid offers high performance in its discriminating capacity to identify TP (sensitivity 87 to 100%, specificity 81 to 97%). Adenosine deaminase expresses the sum of two isoenzymes (ADA1 and ADA2). ADA1 is ubiquitous in all cells, including lymphocytes and monocytes, whereas ADA2 is found only in monocytes. Analysis and determination of these isoenzymes have shown that ADA in TP increases particularly at the expense of ADA2 and that the ADA1 /ADAp activity ratio improves performance in terms of sensitivity, specificity, and efficacy (100%, 92 to 97%, and 98%, respectively) in correcting all false-negative and false-positive results except 1 to 9% of nonlymphoproliferative malignancies. Only the high performance of ADA in the identification of TP allows it to be assumed that pleural biopsy can be obviated, especially in patients aged less than 35 years of age or having a lymphocyte-to-neutrophil proportion of more than 0.75 in regions of high prevalence. Quick determination and low cost justify its routine use in exudates. The ADA1 /ADAp activity ratio improves performance even more and could be used in cases with uncertain diagnoses or in regions with low prevalence of tuberculosis.     

结核性胸膜炎发生胸膜肥厚因素的探讨

目的 探讨结核性胸膜炎发生胸膜肥厚的因素?方法 对1993 年至1995 年收治的113 例结核性胸膜炎发生胸膜肥厚的原因进行分析?结果 胸膜肥厚的发生与就诊时间?胸水细胞数与蛋白含量及胸穿抽液是否及时有关, 与胸水量无关?结论 降低结核性胸膜炎发生胸膜肥厚的重要措施: 1 . 积极抗结核治疗及积极胸穿抽液, 2 . 归口管理?     

C-reactive protein in lymphocytic pleural effusions: a diagnostic aid in tuberculous pleuritis

BACKGROUND: C-reactive protein (CRP) pleural fluid levels have been found to be higher in tuberculosis and parapneumonic effusions than in other causes of pleural effusion. OBJECTIVE: The aim of this study was to analyze whether CRP (a simple and inexpensive test) may be a diagnostic aid for tuberculosis in lymphocytic pleural effusions. METHODS: One hundred and forty-four patients with a lymphocytic pleural effusion (more than 50% lymphocytes in the differential white blood cell count) were included. The patients were 93 men (65%) and 51 women (35%), aged 64 +/- 18 years (mean +/- SD). The diagnoses were as follows: tuberculosis, 20; pleural effusion associated with malignancy, 69; transudates, 38; other benign exudates, 17. RESULTS: The CRP pleural fluid level was higher in tuberculous pleuritis (54 +/- 24 mg/l) than in lymphocytic effusions of other origin (21 +/- 16 mg/l; p < 0.001). High CRP levels (>or=50 mg/l) have a high specificity for tuberculosis (95%), and low levels (<30 mg/l) have a high sensitivity (95%) for excluding disease. CONCLUSIONS: CRP pleural fluid level determination is useful in the diagnostic workup of lymphocytic pleural effusions. High CRP levels are very suggestive of tuberculous pleuritis, and low CRP levels make this diagnosis unlikely.     

胸膜活检标本行基因扩增对结核性胸膜炎的诊断价值

目的 评价胸膜活检组织行聚合酶链反应(PCR)对结核性胸膜炎的诊断价值?方法 PCR检测65例胸膜活检组织中结核分枝杆菌DNA,并与胸水检测及胸膜活检组织病检对比?结果 胸膜活检组织PCR阳性率831%,胸水PCR阳性率为631%,胸膜活检组织病检阳性率为60.0%?前者较后两者更敏感?结论 胸膜活检组织PCR检测对结核性胸膜炎有较高的诊断价值?     

北京市昌平区高校新入学学生结核菌素反应强度及患病调查

目的了解北京市昌平区高校大学新生结核菌素反应及患病状况，以便采取相应的措施。方法对2004年9月-2006年9月昌平辖区范围内高校的每年入学新生进行连续3年的结核菌素（PPD）试验；对结核菌素试验强阳性者摄X线胸片及查痰，掌握活动性病例及菌阳病例。结果3年来在昌平辖区内共计给21所高校的大学新生做PPD试验139136人次，查出活动性肺结核患者226例，结核性胸膜炎44例，陈旧性肺结核患者46例，其中痰涂片阳性患者16例，痰培养仅阳性患者3例。通过连续3年的观察表明，每年高校入学新生PPD≥15mm者分别占受调查总数的16．5％、17．6％、17．7％，提示新大学生受结核菌感染及患病情况较严重。结论应把大学生列为结核病防治重点对象之一。加强入学时的检查，及时发现病人彻底治疗，预防传染。     

北京市昌平区高校新入学学生结核菌素反应强度及患病调查

目的了解北京市昌平区高校大学新生结核菌素反应及患病状况,以便采取相应的措施。方法对2004年9月—2006年9月昌平辖区范围内高校的每年入学新生进行连续3年的结核菌素(PPD)试验;对结核菌素试验强阳性者摄X线胸片及查痰,掌握活动性病例及菌阳病例。结果3年来在昌平辖区内共计给21所高校的大学新生做PPD试验139136人次,查出活动性肺结核患者226例,结核性胸膜炎44例,陈旧性肺结核患者46例,其中痰涂片阳性患者16例,痰培养仅阳性患者3例。通过连续3年的观察表明,每年高校入学新生PPD≥15mm者分别占受调查总数的16.5%、17.6%、17.7%,提示新大学生受结核菌感染及患病情况较严重。结论应把大学生列为结核病防治重点对象之一。加强入学时的检查,及时发现病人彻底治疗,预防传染。     

Clinical immunology of tuberculosis

The standard tuberculin skin test has been known as the prototype of delayed type hypersensitivity testing which is mediated by T cells and macrophages and plays an important role in the pathogenesis of tuberculosis. Tuberculosis is indeed a chronic infectious disease, but variation in the host immune responses to tubercle bacilli results in the various clinical manifestations of the disease ranging from an immunologically hyperreactive state observed in pleural fluid lymphocytes in tuberculous pleurisy to an almost totally unresponsive state observed in those severely ill with refractory tuberculosis. In tuberculous pleurisy, T cells in pleural fluid respond remarkably in vitro to PPD tuberculin whereas T cells in peripheral blood responded poorly to PPD stimulation. Compartmentalization of PPD-reactive T cells in the pleural fluid and immunosuppression by T cells and/or macrophages in the peripheral blood were responsible for this immunological difference observed between the lymphocytes in pleural fluid and those in peripheral blood of tuberculous pleurisy. In advanced, drug-resistant tuberculosis as well as in nontuberculous mycobacterial infection, the proliferative responses of T cells in vitro to PPD stimulation were impaired. This depressed T cell response was due to depressed interleukin-2 (IL-2) production and not due to depressed IL-2 responsiveness. Therefore, the addition of exogenous IL-2, returned the depressed PPD-induced lymphocyte proliferation in vitro in these patients to the level of the response observed in lymphocytes from patients with newly-diagnosed tuberculosis. Our results suggest that recombinant IL-2 offers a novel approach to the therapy of advanced, drug-resistant tuberculosis and nontuberculous mycobacterial infection. Preliminary clinical trials of immunotherapy with recombinant IL-2 reveals the effectiveness of this therapy and encourages us to extend the trial to a larger scale. Tubercle bacilli have various biological activities. Research on tuberculosis and tubercle bacilli have contributed much to the progress of biochemistry, pathology and immunology. Mycobacterium is a fascinating organism, which now presents another big appeal to those studying immunology: Study of immunological interaction between gamma delta T cells and the highly conserved protein in mycobacteria, HSP, heat shock protein will contribute to the elucidation of the mechanism of immunological surveillance and the mechanism of autoimmune diseases. In addition, it will also contribute to the development of a new mycobacterial vaccine which will give direct, protective immunity against tuberculosis.     

Diagnostic significance of interferon-gamma in tuberculous pleural effusions

STUDY OBJECTIVES: Tuberculosis (TB), the single most frequent infectious cause of death worldwide, also is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Differential diagnosis between TB and nontuberculous pleural effusion can be sometimes difficult, representing a critically important clinical problem. METHODS: We studied 46 patients presenting with pleural effusion to the National Sanyo Hospital between April 2000 and January 2001 (34 men and 12 women; mean age, 64 years). Ten patients (22%) had tuberculous pleurisy, 19 patients (41%) had malignant pleuritis, and 17 patients (37%) had pleural effusion due to an etiology other than tuberculosis or cancer. Pleural fluid concentrations of four suggested markers were measured using commercially available kits. RESULTS: The pleural fluid levels (mean +/- SE) of adenosine deaminase (83.3 +/- 18.2 U/L vs 25.8 +/- 20.4 U/L, p < 0.0001), interferon-gamma (137 +/- 230 IU/mL vs 0.41 +/- 0.05 IU/mL, p < 0.0001), immunosuppressive acidic protein (741 +/- 213 micro g/mL vs 445 +/- 180 micro g/mL, p < 0.001) and soluble interleukin 2 receptor (7,618 +/- 3,662 U/mL vs 2,222 +/- 1,027 U/mL, p < 0.0001) were significantly higher for tuberculous pleuritis than for other causes of effusion. Receiver operating characteristic analysis demonstrated that pleural fluid content INF-gamma was the best indicator of tuberculous pleurisy among four relevant biological markers. CONCLUSIONS: INF-gamma in pleural fluid is the most sensitive and specific among four biological markers for tuberculous pleuritis. Thus, our results suggest that determination of INF-gamma at the onset of pleural effusion is informative for the diagnosis of tuberculous pleuritis. Further studies including larger numbers of patients are needed to verify this result.     

Simultaneous measurements of adenosine deaminase activity and tuberculostearic acid in pleural effusions for the diagnosis of tuberculous pleuritis.

Adenosine deaminase (ADA) activity and tuberculostearic acid (TSA) levels in pleural effusions were measured in 18 patients with active tuberculous pleuritis, 16 patients suspected of having tuberculous pleuritis, 14 patients with carcinomatous pleuritis, and 19 patients suffering from pleuritis of non-malignant and non-tuberculous etiology. In the patients with active tuberculous pleuritis, ADA was elevated in 56% and TSA was positive in 78%. In 83% of these patients, either ADA was elevated or TSA was positive. ADA was elevated together with a positive TSA in 50%. In contrast, TSA was positive in only 6% and ADA was elevated in 24% of the patients with non-tuberculous pleuritis, and none of these patients showed the combination of an elevation of ADA and a positive TSA. These results suggest that simultaneous measurements of both ADA and TSA in pleural effusions are useful for the diagnosis of tuberculous pleuritis.     

结核性胸膜炎的临床特征(附345例分析)

目的　进一步了解结核性胸膜炎的临床特点及其与肺结核的关系。方法 对345例结核性胸膜炎病人的临床特征进行回顾性分析。结果 ①年龄分布,<35岁占51.6%,≥55岁占23.2%,平均38.1岁。②发热、咳嗽、胸痛的发生率分别为73.6%、57.7%和51.9%。③单侧胸水占93.0%,双侧胸水占7.0%,左、右侧发生率分别为47.8%及45.2%。④中、小量胸水共占94.5%,大量胸水仅占5.5%。⑤胸膜炎同时合并肺结核占47.8%。⑥胸水呈草黄色占89.6%,呈血性占10.4%。⑦胸水结核菌检出率为3.2%。⑧PPD试验阳性反应者占83.3%。⑨红细胞沉降率(ESR)增快者占64.9%,均值为46.9mm/1h。结论 结核性胸膜炎仍是目前的常见疾病之一,多见于青少年,与肺结核关系密切,在诊断时应注意其临床特点。