HIV/AIDS人群中肺结核患者的治疗效果与细胞免疫的相关性研究

摘要/Abstract

摘要： 目的了解HIV/AIDS人群中肺结核(HIV(+)TB(+))患者的免疫特征及抗结核治疗的效果。方法横断面收集12例现症HIV(+)TB(+)患者、24例HIV/TB双重感染者(HIV(+)PPD(+))、74例单纯HIV/AIDS患者(HIV(+)PPD(-))、56例单纯肺结核病患者(HIV(-)TB(+))(初治涂阳)及36例正常对照者的外周血2 ml,进行淋巴细胞亚群的比较。同时前瞻性收集12例HIV(+)TB(+)患者及56例HIV(-)TB(+)患者的血常规数据、药物不良反应的发生、痰菌阴转及肺部病变的改变进行抗结核治疗的效果分析。结果(1)与正常人群相比,HIV感染或结核感染均可导致患者的淋巴细胞亚群不同程度的下降(P<0.05)。(2)在HIV与结核双重感染人群的细胞免疫中,与HIV相关的免疫改变起主要作用:不管其是否结核发病,其淋巴细胞计数都存在同等程度的下降。(3)HIV(+)TB(+)患者的抗结核治疗效果较好:与HIV(-)TB(+)患者相比,药物不良反应、痰菌阴转及肺部病变的改变无显著性差异(P>0.05)。结论HIV(+)TB(+)患者的细胞免疫主要与HIV感染有关,而有效的抗结核药物治疗可提高HIV(+)TB(+)患者的细胞免疫功能,并可使其肺结核病得到良好的控制。

关键词: HIV/AIDS, 结核, PPD试验, 细胞免疫, 治疗效果

Abstract: Objective To understand the immunological characteristics and chemotherapy effect of HIV infected patients with tuberculosis. Methods Cross-sectional study was performed to compare the lymphocyte subsets of 12 HIV infected patients with tuberculosis,24 HIV infected patients with latent M.tuberculosis infection,74 patients infected HIV only,56 active pulmonary tuberculosis without HIV infection and 36 normal controls,and data of full blood count,adverse reactions,convert of sputum test and lung pathological changes in HIV-infected patients with tuberculosis disease were prospectively collected to analyse their chemotherapy effect after 6 month therapy. Results(a) Compare to normal controls,both HIV infection and M.tuberculosis infection can result in a decrease of lymphocyte subset count among these patients(P<0.05).(b) Immunology changes correlated with HIV infection predominated among patients co-infected with HIV and M.tuberculosis,and their lymphcyte count decreased similarly whether their tuberculosis disease occurred or not.(c) Anti-tuberculosis therapy was good in HIV-infected patients with tuberculosis.There was no significant difference regarding occurrences of adverse reactions,convert of sputum test and changes of represents of chest radiography between HIV-infected patients with tuberculosis disease and patients with tuberculosis only(P>0.05). Conclusion Cell-mediated immunity of HIV-infected patients with tuberculosis mainly correlates with their HIV infection,and effective anti-tuberculosis therapy can enhance their cellular immune function and control their tuberculosis disease well.

Key words: HIV/AIDS, tuberculosis, purfied protein derivatives tuberculin test(PPD test), cell-mediated immunity, therapeutic efficacy

刘凤仁,汤恒,殷继国,周沛林,叶建君,熊昌富,刘焰东,赵焕虎,叶临湘. HIV/AIDS人群中肺结核患者的治疗效果与细胞免疫的相关性研究[J]. 中国防痨杂志, 2008, 30(4): 311-315.

Liu Fengren1,Tang Heng,Yin Jiguo,et al.. Analysis on anti-tuberculosis efficiancy and cell mediated immunity for HIV-1 infected patients with pulmonary tuberculosis disease[J]. Chinese Journal of Antituberculosis, 2008, 30(4): 311-315.

参考文献

1 Toosi Z, Sierra-Madero JG, Blinkhorn RA, et al. Enhanced susceptibility of blood monocytes from patients with pulmonary tuberculosis to productive infection with human immunodeficiency virus type 1 [J]. J Exp Med(Journal of Experimental Medicine)，1993,177:1511—1516
2 Goletti D, Weissman D, Jackson RW，et al. Effect of Mycobacterium tuberculosis on HIV replication： role of immune activation[J], J Immunol (The Journal of Immunology) , 1996,157(3)：1271-1278
3 Mancino G，Placido R, Bach S，et al. Infection of human monocytes with Mycobacterium tuberculosis enhances human immunodeficiency virus type 1 replication and virus transmission to T cells[J]. J Infect Dis (The Journal of Infectious Diseases), 1997,175:1531—1535
4 Whalen C, Horsburgh CR, Horn D, et al. Accelerated course of human immunodeficiency virus infection after tuberculosis [J].Am J Respir Crit Care Med (American Journal of Respiratory and Critical Care Medicine)，1995, 151(1) : 129 —135
5 Elizabeth L. Corbett, Catherine J. Watt, Neff Walker, et al.The growing burden of tuberculosis： global trends and interactions with the HIV epidemic [J]. Arch Intern Med (Archives of Internal Medicine) , 2003,163：1009-1021
6 Orme IM, Collins FM. Protection against Mycobacterium tuberculosis infection by adoptive immunotherapy. Requirement for T Medicine) 1983; 158:74-83
7 Kaplan G，Freedman VH. The role of cytokines in the immune response to tuberculosis[J]. Res Immunol ( Research in Immunology) , 1996 , 147(8):565-572
8 Kaufmann SH, Ladel CH. Role of T cell subsets in immunity against intracellular bacteria：experimental infections of knock-out mice with Listeria monocytogenes and Mycobacterium bovis BCG [J]. Immunobiology 1994, 191:509 — 519
9 Vanham G，Edmonds K，Qing L et al. Generalized immune activation in pulmonary tuberculosis： co-activation with HIV infection[J]. Clin Exp Immunol (Clinical and Experimental Immunology) , 1996’ 103(1):30 —34
10 Pedrazzini T, Louis JA. Functional analysis in vitro and in vivo of Mycobacterium bovis strain BCG-specific T cell clones[J]. J ImmunoKThe Journal of Immunology) 1986，136(5)： 1828-1834
11 Orme IM. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection [J]. J Immunol (The Journal of Immunology) 1988；140:3589 — 93
12 Onwubalili JK, Edwards AJ, Palmer. L. T4 lymphopenia in human tuberculosis[J]. Tubercle 1987；68(3) ： 195 —200
13 Swanson Beck J，Potts RC, Kardjito T，et al. T4 lymphopeniain patients with active pulmonary tuberculosis[J]. Clin Exp Immunol(Clinical & Experimental Immunology) 1985, 60(1):49-54
14 Singhal M, Banavalikar JN, Sharma S, et al. Peripheral blood T lymphocyte subpopulations in patients with tuberculosis and the effect of chemotherapy[J], Tubercle 1989, 70(3) ： 171-178
15 Jones BE, Oo MM, Taikwel EK et al. CD4 cell counts in human immunodeficiency virus-negative patients with tuberculosis[J]. Clin Infect Dis (Clinical Infectious Diseases, 1997，24(5),988-991
16 Akayama E, Koike Y, Ohkawa T et al. Functional and Vbeta repertoire characterization of human CD8 + T — cell subsets with natural killer cell markers, CD56 + CD57— T cells, CD56+ CD57+ T cells and CD56 —CD57+ T cells[J]. Immunology, 2003, 108(2)s211-219
17 Flynn JL, Chan J, Triebold KJ, et al. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection[J].J Exp Med(Journal of Experimental Medicine)1993,178(6) ,2249-2254
18 Hirsch CS，Toossi Z, Vanham G et al. Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis[J]. J Infect Dis (The Journal of Infectious Diseases)，1999 , 179(4):945 — 953
19 Ainslie，GM，Solomon J A, Bateman ED. Lymphocyte and lymphocyte subset numbers in blood and in bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis at presentation and during recovery[J]. Thorax, 1992,47(7):513-518
20 Hoheisel，GB, Tabak L, Teschler H，et al. Bronchoalveolar lavage cytology and immunocytology in pulmonary tuberculosis[J]. Am. J. Respir. Crit. Care Med (American Journal of Respiratory and Critical Care Medicine) , 1994, 149(2) :460—463
21 Law KF, Jagirdar J, Weiden MD, et al. Tuberculosis in HIV-positive patients： cellular response and immune activation in the lung[J]. Am. J. Respir. Crit. Care Med(American Journal of Respiratory and Critical Care Medicine), 1996, 153(4) :1377-1384
22 Urdaneta, E，Feo-Figarella E，Montalvo C，et al. Characterization of local memory cells in stage-classified pulmonary tuberculosis： preliminary observations[J]. Scand. J. ImmunoK Scandinavian Journal of Immunology), 1998*47(5) :496 —501
23 Yu C-T, Wang C-H, Huang T-J, et al. Relation of bronchoalveolar lavage T lymphocyte subpopulations to rate of regression of active pulmonary tuberculosis[J]. Thorax, 1995，50(8) ：869-874
24 Schluger NW, Rom WN. The host immune response to tuberculosis[J]. Am. J. Respir. Crit. Care Med(American Journal of Respiratory and Critical Care Medicine) , 1998,157(3) ： 679-691
25 Takashima T，Ueta C, Tsuyuguchi I，et al. Production of tumor necrosis factor alpha by monocytes from patients with pulmonary tuberculosis[J], Infect ImmunCInfection and Immunity) ,1990, 58(10):3286—3292
26 Hertoghe T, Wajja A, Ntambi L，et al. T cell activation, apoptosis and cytokine dysregulation in the (co) pathogenesis of HIV and pulmonary tuberculosis (TB) [J]. Clin Exp Immunol (Clinical Experimental Immunology) , 2000, 122(3):350 —357
27 Veenstra H, Baumann R, Carroll NM, et al. Changes in leucocyte and lymphocyte subsets during tuberculosis treatment；prominence of CD3dimCD56 + natural killer T cells in fast treatment responders[J]. Clin Exp Immunol (Clinical & Experimental Immunology), 2006, 145(2)： 252 — 260
28 Girardi E，Palmieri F，Cingolani A, et al. Changing clinical presentation and survival in HIV-associated tuberculosis after highly active antiretroviral therapy[J]. J Acquir Immune Defic Syndr (Journal of Acquired Immune Deficiency Syndromes),2001, 26(4)：326-331
29 Weis SE, Slocum PC, Blais FX, et al. The effect of directly observed therapy on the rates of drug ressitance and relapse in tuberculosis[j].N.Enel.J.Med(The New England Journal Of Medicine). 1994, 330(17), 1179-1184
30 Fitzgerald DW, Desvarieux M, Severe P, et al. Effect of posttreatment isoniazid on prevention of recurrent tuberculosis in HIV-l-infected individuals： a randomised trial [J]. Lancet,2000, 356(9240),1470-1474

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