NK cells play an important role in the control of tuberculosis infection: they are not only able to kill the infected cells, but also control the activity of macrophages and development of the adaptive immune response. Still, there is little information on the role of specific NK cell subsets in this network. In this study, we focused on the mycobacteria-driven responses of the NK cells expressing HLA-DR – a type of MHC class II. We have revealed that this subset is increased in the peripheral blood of patients with primary diagnosed tuberculosis, and expands in response to in vitro stimulation with ultrasonically destroyed Mycobacterium tuberculosis cells (sonicate). The expanded HLA-DR+ NK cells had less differentiated phenotype, higher proliferative activity and increased expression of NKp30 and NKp46 receptors. HLA-DR+CD56dim NK cells showed higher IFNγ production and degranulation level than the respective HLA-DR− NK cells in response to both 24 h and 7 day stimulation with sonicate, while HLA-DR+CD56bright NK cells mostly demonstarted similar high responsiveness to the same stimulating conditions as their HLA-DR−CD56bright counterparts. After preliminary incubation with destroyed mycobacteria, cytokine-activated HLA-DR-expressing NK cells were able to mediate mycobacteria-induced and HLA-DR-dependent cytokine production in autologous CD4+ T cells. Thus, functionally active HLA-DR+ cells seem to be one of the NK cell subsets providing an important link to the adaptive immunity.
IFN-γ is a key cytokine in antituberculosis (TB) defense. However, how the levels of its secretion affect M. tuberculosis (Mtb) infection is not clear. We have analyzed associations between IFN-γ responses measured in QuantiFERON®-TB Gold In-tube (QFT) assay, TB disease severity, and Mtb infection activity. TB severity was evaluated based on the results of radiological, microbiological, and clinical examinations. Antigen-driven IFN-γ secretion did not correlate with TB severity. Mitogen-induced IFN-γ secretion correlated inversely with the form of pulmonary pathology and the area of affected pulmonary tissue; the levels of spontaneous IFN-γ secretion correlated with patients' age (r = 0.395, p = 0.001). Mtb infection activity was evaluated based on radiological data of lung tissue infiltration, destruction, dissemination or calcification, and condensation. The rate of positive QFT results and the levels of antigen-driven IFN-γ secretion increased in a row: patients with residual TB lesions < patients with low TB activity < patients with high TB activity. Thus, antigen-driven IFN-γ secretion and QFT results did not associate with TB severity but associated with the infection activity. The results suggest that quantitative parameters of IFN-γ secretion play a minor role in determining the course of TB disease but mirror the activity of the infectious process.
Background: The early identification of Mycobacterium tuberculosis infection can prevent tuberculosis (TB) transmission. A skin test with a tuberculosis recombinant allergen (Diaskintest) is a new method for identification that has been implemented in Russia. This study was performed to compare the performances of Diaskintest and QuantiFERON-TB Gold (QFT) in adults and children with suspected TB in Moscow, Russia. Methods: Adults (n = 85) and children (n = 96) were tested using Diaskintest and QFT. Concordance and comparative analyses were performed. Results: Diaskintest and QFT were concordant in 84% of adults and 90% of children (overall concordance 87%, k > 0.6, K c > 0.5). The concordance between QFT, Diaskintest, and the final diagnosis was good in adults (86% and 81%, respectively) and moderate in children (77% and 79%, respectively). In adults, QFT had a higher sensitivity for detecting TB than Diaskintest (82% and 68%, respectively); in children, Diaskintest was more sensitive (73% and 65%, respectively). In patients with a confirmed TB diagnosis, negative Diaskintest/QFT results were associated with low disease activity. Combined Diaskintest/QFT results identified TB patients with higher sensitivity and specificity than each test separately. Conclusions: Diaskintest is a low-cost diagnostic tool that shows a test positivity rate similar to QFT and can be used in combination with QFT as an adjunctive test for TB diagnosis. (O.V. Kasimceva), hergertv@mail.ru (V.Y. Gergert), cniit@ctri.ru (A. Ergeshov), ivlyadova@mail.ru (I.V. Lyadova).
ФГБНУ «Центральный научно-исследовательский институт туберкулеза», Москва, РоссияЦель: исследование эффективности профилактики возникновения медиастинальной грыжи (МСГ) и эффективности коррекции имевшейся до операции МСГ путем пластики переднего средостения (ППС) во время проведения пневмонэктомии (ПЭ)� Материалы и методы. Результаты ПЭ у 30 пациентов (22 мужчины и 8 женщин, возраст от 20 до 56 лет) с фиброзно-кавернозным туберку-лезом легких с множественной/широкой лекарственной устойчивостью возбудителя� В 1-й группе -17 пациентов, которым проведена ПЭ с ППС, из них у 10 (58,8%) пациентов до операции не было МСГ, а у 7 (41,2%) пациентов уже была МСГ малого объема� Во 2-й группе -13 пациентов, у которых ПЭ не сопровождалась ППС� Результаты. При ПЭ МСГ не формируется: у 82,4% (95%-ный ДИ 59,0-93,8%) пациентов, если выполняется ППС, и у 7,7% (95%-ный ДИ 1,4-33,3%) пациентов, если пластика не используется, p < 0,01� Проведение ППС во время ПЭ устранило имевшуюся до операции МСГ малого размера у 71,4% (95%-ный ДИ 35,9-91,8%) пациентов, вы-полнив коррекционную функцию� После ПЭ по поводу фиброзно-кавернозного туберкулеза риск формирования МСГ у пациентов, не имевших ее до операции, при выполнении пластики средостения составляет 10,0% (95%-ный ДИ 1,8-40,4%), у имевших МСГ -28,6% (95%-ный ДИ 8,2-64,1%)� При неиспользовании ППС риск составляет 90,0% (95%-ный ДИ 59,6-98,2%)� Ключевые слова: хирургия туберкулеза, осложнения пневмонэктомии, медиастинальная грыжа, пластика переднего средостения ANTERIOR MEDIASTINAL PLASTICS DURING PNEUMONECTOMY AS PREVENTION AND TREATMENT OF A MEDIASTINAL HERNIA IN FIBROUS CAVERNOUS PULMONARY TUBERCULOSIS PATIENTS M. А. BАGIROV, E. V. KRАSNIKOVА, А. E. ERGESHOVА, O. V. LOVАCHEVА, N. L. KАRPINА, R. А. PENАGI Central Research Institute of Tuberculosis, Moscow, RussiaThe objective is to study the efficiency of prevention of a mediastinal hernia and efficiency of its treatment through anterior mediastinal plastics performed during pneumonectomy� Subjects and Methods� Results of pneumonectomies in 30 patients (22 men and 8 women at the age varying from 20 to 56 years old) with fibrous cavernous pulmonary tuberculosis with multiple or extensive drug resistance� Group 1 included 17 patients who had pneumonectomy with anterior mediastinal plastics, of them 10 (58�8%) had no mediastinal hernia and 7 (41�2%) patients had a minor one� Group 2 included 13 patients who had pneumonectomy without anterior mediastinal plastics� Results. When pneumonectomy was performed, no mediastinal hernia developed in 82�4% (95% CI 59�0-93�8%) of patients who had anterior mediastinal plastics and in 7�7% (95% CI 1�4-33�3%) of patients with no plastics, p < 0�01� Anterior mediastinal plastics performed during pneumonectomy repaired a minor mediastinal hernia in 71�4% (95% CI 35�9-91�8%) of patients� After pneumonectomy with anterior mediastinal plastics due to fibrous cavernous tuberculosis, the risk of mediastinal hernia made 10�0% (95% CI 1�8-40�4%) in the patients who had no hernia before surgery, while in the patie...
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