Tuberculosis (TB) is one of the most common infections worldwide. Eradication of an intracellular pathogen M. tuberculosis requires to induce a Th1 response by activating IFNγ-producing tissue macrophages. Along with Th1 cells, various subsets of Th17 and follicular T-helper cells (Tfh) able to secrete a broad range of cytokines, including IFNγ, can also be involved in eliminating bacterial pathogens. It justified analyzing in this study changes in percentage of various peripheral blood Th subsets, including Th1, Th2, Th17 and Tfh cells, in TB patients. For this, major CD3+CD4+T cell subsets were assessed by using multicolor flow cytometry in TB patients (n = 40) and healthy volunteers (n = 30). It was found that in TB patients vs. control group percentage of peripheral blood CD45RA–CCR7+ central memory (CM) Th was decreased also affecting frequency of some functional T cell subsets, e.g. either lowering Th2 cells (9.11% (6.95; 13.77) vs. 7.21% (5.64; 9.84), p = 0.012) or elevating CCR6+ Th17 subsets (35.92% (27.72; 41.06) vs. 40.39% (35.41; 47.79; p = 0.016), respectively, but not influencing Th1 and Tfh subsets frequencies. Moreover, percentage of total CCR6+CM Th cells in TB patients vs. control was decreased in CCR4–CXCR3+Th17.1 cell subset (42.87% (33.64; 49.45) vs. 52.26% (46.45; 56.95), p < 0.001), whereas standard CCR4+CXCR3–Th17 and CCR6+ DP Th17 subsets were elevated (p = 0.005 and p = 0.002, respectively). In addition, altered Tfh subset composition associated with the increased (p = 0.021) percentage of CXCR3–CCR6–Tfh2 cells, but decreased CXCR3+CCR6–Tfh1 cells (p = 0.036) was observed. Finally, frequency of peripheral blood Th subsets noted above was also analyzed within effector memory (CD45RA–CCR7–) cells. It was found that in TB patients vs. volunteers frequency of Th17.1 cells was also significantly lower (p = 0.006) in CCR6+EM Th (54.43% (41.19; 91.92) vs. 61.76% (54.01; 65.63), whereas percentage of double-positive Th17 was significantly increased (20.83% (15.12; 30.87) and 12.93 % (9.80; 19.01), respectively, p < 0.001). Thus, it suggests that during M. tuberculosis infection percentage of IFNγ-producing Th17 and Tfh cells was reduced compared to control group also affecting both central memory Th cells patrolling peripheral lymphoid organs as well as effector memory Th cells able to exit to site of infection.
Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases.
Выводы: полученные в исследовании данные могут быть применены не только в диагностике активного туберкулеза при отсутствии верификации диагноза, но также позволяют выделить группу высоко риска по развитию заболевания у лиц с латентной туберкулезной инфекцией.
ЭФФЕКТИВНОСТЬ ТЕРАПИИ ТУБЕРКУЛЕЗА ЛЕГКИХ С СОХРАНЕННОЙ ЛЕКАРСТВЕННОЙ ч у в с т в и т е л ь н о с т ь ю м и к о б а к т е р и й м. в. П а в л о в а 1, и. в. ч е р н о х а е в а 1, а. а. с т а р ш и н о в а 1, н. в. с а п о ж н и к о в а 1, е. н. Б е л я е в а 1-3, а. л. ч у ж о в 1-2 'Ф ГБУ «сан к т-п етер бургск и й Н И И фтизиопульмонологии», санкт-И етербург 2с п б ГБУЗ «пуш кинский противотуберкулезны й диспансер», санкт-И етербург 3ГУЗ «Городская противотуберкулезная больница», санкт-И етербург Статья посвящ ена изучению сравнительной эф фективности ф еназида (изоникотиноилгидразин-О ,№) ж елеза (II) сульфат дигидрат и изониазида у больных туберкулезом легких с сохраненной лекарственной чувствительностью возбудителя. П олучена высокая эффективность лечения «значительное улучш ение» и «улучшение» у пациентов 1-й группы-81,4%, что сопоставимо со стандартной схемой терапии (85,7%) во 2-й группе. Общее число нежелательных побочных реакций в основной группе отмечалось достоверно реже-18,6% против 33,9%, p < 0,05. Гепатотоксические реакции с повышением в 2-3 раза уровня аланинтрансаминазы зареги стрированы значительно реже (9,3%) в I группе по сравнению с группой получавших изониазид-23,2%. Ключевые слова: туберкулез, лекарственная чувствительность МБТ, лечение, (изоникотиноилгидразин-О,№) ж елеза (II) сульфат дигидрат, гидразид изоникотиновой кислоты. TREATMENT EFFICIENCY OF DRUG SUSCEPTIBLE PULMONARY TUBERCULOSIS m. v p a v l o v a 1, i. v c h e r n o k h a e v a 1, a. a. s t a r s h i n o v a 1, n. v s a p o z h n i k o v a 1, e. n. b e l y a e v a 1-3, a. l. c h u z h o v 1-2 1s t. petersb urg r e s e a r c h in stitu te of phthisiopulm onology, s t. petersburg, r u ss ia 2pu sh kin TB d isp en sary, s t. petersburg, r u ss ia M u n icip al TB h o sp ita l, s t. petersb urg, r u ss ia The article describes the study of comparative efficiency of fenazid (isonicotinoilhydrazine-0,N ') ferrous dihydrate sulphate (II) and isoniazid in drug susceptible pulm onary tuberculosis patients. The high treatm ent efficiency namely significant im provem ent and im provem ent was observed in the patients of Group 1-84.1% w hich could be compared to the standard treatm ent regim en (85.7%) in Group 2. The total num ber of adverse reactions in the main group was confidently lower-18.6% against 33.9%, p < 0.05. H epatotoxic reactions w ith 2-3 fold increase of alaninetransferase level was registered significantly less (9.3%) in Group 1 compared to the Group treated w ith isoniazid.
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