母牛分枝杆菌菌苗对HIV感染合并结核分枝杆菌潜伏感染者外周血T细胞亚群的影响

doi:10.19982/j.issn.1000-6621.20230124

中国防痨杂志 ›› 2023, Vol. 45 ›› Issue (10): 925-931.doi: 10.19982/j.issn.1000-6621.20230124

母牛分枝杆菌菌苗对HIV感染合并结核分枝杆菌潜伏感染者外周血T细胞亚群的影响

杨正贵¹(), 蒋泽顺², 刘兰³, 韩雪⁴

¹宁夏回族自治区第四人民医院结核病防治科,银川 750021
²西安市疾病预防控制中心结核病预防控制科,西安 710061
³宁夏医科大学公共卫生学院流行病与卫生统计学系,银川 750004
⁴宁夏回族自治区第四人民医院感染性疾病科,银川 750021

收稿日期:2023-04-17 出版日期:2023-10-10 发布日期:2023-10-07
通信作者: 杨正贵,Email:yangzhenggui_1983@126.com
基金资助:
宁夏回族自治区重点研发计划项目(2020BEG03018);中国公共卫生联盟(第一批)课题(GWLM202021);宁夏回族自治区卫生健康委员会科研课题(2021-NW-031)

Effect of Mycobacterium vaccinae on T Lymphocyte subsets in peripheral blood of HIV patients complicated with latent Mycobacterium tuberculosis infection

Yang Zhenggui¹(), Jiang Zeshun², Liu Lan³, Han Xue⁴

¹Department of Tuberculosis Prevention and Control, the Fourth People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, China
²Department of Tuberculosis Prevention and Control, Xi’an Center for Disease Control and Prevention, Xi’an 710061, China
³Department of Epidemiology and Health Statistics, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
⁴Department of Infectious Diseases, the Fourth People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, China

Received:2023-04-17 Online:2023-10-10 Published:2023-10-07
Contact: Yang Zhenggui, Email: yangzhenggui_1983@126.com
Supported by:
Key Research and Development Program of Ningxia Hui Autonomous Region(2020BEG03018);China Public Health Alliance (First Batch) Project(GWLM202021);Research Project of Ningxia Hui Autonomous Region Health Commission(2021-NW-031)

摘要/Abstract

摘要：

目的: 探讨母牛分枝杆菌菌苗对HIV合并结核分枝杆菌潜伏感染(latent tuberculosis infection,LTBI)者T细胞亚群的影响及其使用的安全性。方法: 采用多中心前瞻性队列研究方法,连续纳入2003年6月至2020年6月宁夏回族自治区银川市AIDS管理机构管理的经结核菌素皮肤试验筛查确诊的96例HIV感染合并LTBI者作为研究对象。研究对象按照银川市所辖县区划分为试验组(63例)和对照组(33例)。试验组在高效抗逆转录病毒治疗的基础上,注射母牛分枝杆菌菌苗22.5μg/次,每2周注射1次,共3次。对照组在高效抗逆转录病毒治疗的基础上,口服异烟肼300mg/次,1次/d,连续服用6个月。于治疗前和治疗结束后1个月、3个月随访时,检测并比较两组研究对象的CD4⁺、CD8⁺、CD3⁺T细胞等免疫细胞水平及肝功能指标变化情况;同时,评价两组研究对象不良反应发生情况。结果: 试验组在治疗结束后1个月,CD3⁺T细胞水平为(1583.83±584.69)个/μl,明显高于治疗前 [(1221.20±399.52)个/μl;t=-2.962,P=0.004];治疗结束后3个月,CD3⁺、CD4⁺、CD8⁺ T细胞水平分别为(1816.67±736.86)个/μl、(674.10±282.30)个/μl和(833.21±314.11)个/μl,均明显高于治疗前[分别为(1221.20±399.52)个/μl、(588.71±273.44)个/μl和(609.65±267.71)个/μl],差异均有统计学意义(t=-4.460,P<0.001;t=-2.801,P=0.044;t=-3.801,P<0.001)。治疗结束后3个月,试验组CD3⁺、CD4⁺T细胞水平及CD4⁺/CD8⁺比值(0.86±0.54),均明显高于对照组[分别为(1716.47±689.07)个/μl、(559.11±187.14)个/μl、0.82±0.74],差异均有统计学意义(t=2.209, P=0.034;t=3.666,P=0.008;t=3.502, P=0.001)。在治疗结束后1个月,对照组谷草转氨酶水平为(33.15±11.70)U/L,明显高于试验组[(26.54±9.63)U/L],差异有统计学意义(t=2.624,P=0.011);治疗结束后3个月,对照组谷丙转氨酶[(52.58±27.72)U/L]、谷草转氨酶[(33.74±11.89)U/L]水平均明显高于试验组[(35.29±21.16)U/L、(26.67±11.07)U/L],差异均有统计学意义(t=2.563,P=0.013;t=2.172,P=0.034)。试验组无不良反应,无退出治疗患者,治疗完成率达到100.0%(63/63),明显高于对照组的84.9%(28/33),差异有统计学意义(χ²=7.235,P=0.007)。结论: 母牛分枝杆菌菌苗用于HIV感染合并LTBI者抗结核预防性治疗可提高其细胞免疫水平,且对肝功能的损伤更小,具有较好的安全性。

关键词: 分枝杆菌,结核, 结核菌苗, T淋巴细胞亚群, HIV感染, 前瞻性研究

Abstract:

Objective: To investigate the effects of Mycobacterium vaccinae on T Lymphocyte subsets in HIV patients complicated with latent tuberculosis infection (LTBI) and its safety. Methods: Using a multicenter prospective cohort study method, 96 HIV patients complicated with LTBI who were confirmed through tuberculin skin test screening and managed by the AIDS management agency in Yinchuan City, Ningxia Hui Autonomous Region from June 2003 to June 2020 were continuously included as the study subjects. The research subjects were divided into experimental group (n=63) and control group (n=33) according to the counties and districts. Based on efficient antiretroviral therapy, the experimental group was injected with Mycobacterium vaccinae (22.5 μg, once every two weeks for three times), and the control group received oral isoniazid (300 mg, once a day, continuously for 6 months). Levels of immune cells such as CD4⁺, CD8⁺, and CD3⁺T cells, as well as changes in liver function indicators between the two groups were measured and compared before treatment and at 1-month and 3-month follow-up after treatment. In addition, the occurrence of adverse reactions in both groups was evaluated. Results: One month after the end of treatment, the level of CD3⁺T cells in the experimental group was (1583.83±584.69) cells/μl, significantly higher than that before treatment ((1221.20±399.52) cells/μl; t=-2.962, P=0.004). Three months after the end of treatment, the levels of CD3⁺, CD4⁺, and CD8⁺T cells were (1816.67±736.86) cells/μl, (674.10±282.30) cells/μl and (833.21±314.11) cells/μl, significantly higher than those before treatment ((1221.20±399.52) cells/μl, t=-4.460, P<0.001; (588.71±273.44) cells/μl, t=-2.801, P=0.044; and (609.65±267.71) cells/μl, t=-3.801, P<0.001, respectively). Three months after the end of treatment, the levels of CD3⁺, CD4⁺T cells, and CD4⁺/CD8⁺ ratio (0.86±0.54) in the experimental group were significantly higher than those in the control group ((1716.47±689.07) cells/μl, t=2.209, P=0.034; (559.11±187.14) cells/μl, t=3.666, P=0.008; 0.82±0.74, t=3.502, P=0.001, respectively). One month after the end of treatment, the level of aspartate aminotransferase in the control group was (33.15±11.70) U/L, significantly higher than that in the experimental group ((26.54±9.63) U/L, t=2.624, P=0.011). Three months after the end of treatment, the levels of alanine aminotransferase ((52.58±27.72) U/L) and alanine aminotransferase ((33.74±11.89) U/L) in the control group were significantly higher than those in the experimental group ((35.29±21.16) U/L, t=2.563, P=0.013; and (26.67±11.07) U/L, t=2.172, P=0.034, respectively). The experimental group had no adverse reactions and no patients withdrew from treatment, with a treatment completion rate of 100.0% (63/63), significantly higher than that of the control group (84.9% (28/33), χ²=7.235, P=0.007). Conclusion: The use of Mycobacterium vaccinae for anti-tuberculosis prophylactic treatment in HIV patients complicated with LTBI can improve the cellular immune levels and cause less damage to liver function, indicating good safety.

Key words: Mycobacterium tuberculosis, Tuberculosis vaccines, T-lymphocyte subsets, HIV infections, Prospective studies

中图分类号:

R52
R978.3

杨正贵, 蒋泽顺, 刘兰, 韩雪. 母牛分枝杆菌菌苗对HIV感染合并结核分枝杆菌潜伏感染者外周血T细胞亚群的影响[J]. 中国防痨杂志, 2023, 45(10): 925-931. doi: 10.19982/j.issn.1000-6621.20230124

Yang Zhenggui, Jiang Zeshun, Liu Lan, Han Xue. Effect of Mycobacterium vaccinae on T Lymphocyte subsets in peripheral blood of HIV patients complicated with latent Mycobacterium tuberculosis infection[J]. Chinese Journal of Antituberculosis, 2023, 45(10): 925-931. doi: 10.19982/j.issn.1000-6621.20230124

图/表 3

表1

表2

表3

两组研究对象治疗前及治疗后1个月和3个月肝功能指标变化情况比较

指标	治疗前	治疗后		t值^a	P值^a	t值^b	P值^b
指标	治疗前	1个月	3个月	t值^a	P值^a	t值^b	P值^b
谷丙转氨酶(U/L, $\bar{x} \pm s$)
试验组	32.89±17.75	34.92±22.36	35.29±21.16	-0.868	0.390	-0.989	0.330
对照组	35.87±17.77	44.66±27.03	52.58±27.72	-1.837	0.077	-2.051	0.056
t值	0.759	1.668	2.563
P值	0.450	0.100	0.013
谷草转氨酶(U/L, $\bar{x} \pm s$)
试验组	27.08±9.61	26.54±9.63	26.67±11.07	-0.207	0.837	-0.582	0.564
对照组	27.07±8.97	33.15±11.70	33.74±11.89	-3.167	0.004	-1.604	0.127
t值	-0.008	2.624	2.172
P值	0.994	0.011	0.034
谷丙转氨酶/谷草转氨酶($\bar{x} \pm s$)
试验组	0.94±0.37	0.93±0.41	0.86±0.30	-0.025	0.980	1.460	0.154
对照组	0.81±0.19	0.88±0.35	0.73±0.28	-0.980	0.336	1.176	0.256
t值	-1.893	-0.482	-1.479
P值	0.062	0.631	0.145
碱性磷酸酶(U/L, $\bar{x} \pm s$)
试验组	88.01±24.26	79.43±28.96	68.60±46.33	1.866	0.087	1.867	0.072
对照组	98.93±25.14	86.06±23.08	78.46±26.80	3.439	0.002	5.533	<0.001
t值	1.960	0.807	0.835
P值	0.054	0.424	0.407
谷氨酰胺氨基转移酶(U/L, $\bar{x} \pm s$)
试验组	49.43±26.32	46.53±31.31	55.54±38.67	-0.426	0.677	-1.795	0.084
对照组	50.35±34.58	71.18±61.90	64.78±48.72	-2.105	0.045	2.602	0.019
t值	0.137	1.435	0.763
P值	0.891	0.159	0.449
总胆红素(μmol/L, $\bar{x} \pm s$)
试验组	11.40±3.18	10.79±3.43	10.35±2.47	1.467	0.152	2.531	0.016
对照组	10.30±6.20	9.89±2.98	9.44±3.08	0.555	0.584	0.817	0.425
t值	-0.458	-1.122	-1.180
P值	0.648	0.266	0.243
白蛋白(g/L, $\bar{x} \pm s$)
试验组	45.63±2.74	46.78±3.53	47.58±2.66	-1.737	0.108	-4.661	<0.001
对照组	47.09±3.84	45.67±2.78	47.54±3.10	2.477	0.024	-0.692	0.498
t值	1.889	-1.014	-0.049
P值	0.065	0.319	0.961

表3

参考文献 15

[1]	中华医学会感染病学分会艾滋病丙型肝炎学组, 中国疾病预防控制中心. 中国艾滋病诊疗指南(2018年版). 中华内科杂志, 2018, 57(12): 867-884. doi:10.3760/cma.j.issn.0578-1426.2018.12.002.
[2]	中华医学会感染病学分会艾滋病学组, 中华医学会热带病与寄生虫学分会艾滋病学组. HIV合并结核分枝杆菌感染诊治专家共识. 中华临床感染病杂志, 2017, 10(2): 81-90. doi:10.3760/cma.j.issn.1674-2397.2017.02.001.
[3]	Stanford JL, Bahr GM, Rook GA, et al. Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis. Tubercle, 1990, 71(2): 87-93. doi:10.1016/0041-3879(90)90002-p. pmid: 2219469
[4]	肖彤洋, 李晓琴, 闫宇涵, 等. 母牛分枝杆菌与结核分枝杆菌和卡介苗的交叉免疫应答研究. 中华微生物学和免疫学杂志, 2019, 39(3): 212-216. doi:10.3760/cma.j.issn.0254-5101.2019.03.010.
[5]	Matthews DM, Jenks SM. Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice. Behav Processes, 2013, 96: 27-35. doi:10.1016/j.beproc.2013.02.007.
[6]	刘敏. 母牛分支杆菌菌苗在初治肺结核治疗中的作用. 国际感染杂志(电子版), 2019, 8(2): 18-19.
[7]	杨清銮, 阮巧玲, 张文宏. HIV感染人群潜伏性结核感染筛查与预防性治疗. 临床内科杂志, 2019, 36(11): 729-732. doi:10.3969/j.issn.1001-9057.2019.11.004.
[8]	方刚, 顾小燕, 尹小芳. 母牛分枝杆菌菌苗辅助抗结核方案治疗肺结核对患者免疫功能及疾病转归的影响. 中国临床研究, 2020, 33(4):501-504. doi:10.13429/j.cnki.cjcr.2020.04.017.
[9]	安慧茹, 吴雪琼. 结核病免疫辅助治疗现状与挑战. 中国防痨杂志, 2022, 44(10):983-986. doi:10.19982/j.issn.1000-6621.20220346.
[10]	中华人民共和国国家卫生和计划生育委员会. WS 288—2017 肺结核诊断. 2017-11-09.
[11]	孙照平, 刘辉, 刘荣. 母牛分枝杆菌预防性治疗潜伏性结核感染的效果评价. 现代预防医学, 2013, 40(15): 2894-2896.
[12]	肖静, 韩俊燕, 栗翠林, 等. 抗逆转录病毒治疗时长对HIV/AIDS患者机体代谢的影响. 中华实验和临床病毒学杂志, 2021, 35(2):152-157. doi:10.3760/cma.j.cn112866-20210130-00021.
[13]	Matyanga CMJ, Morse GD, Gundidza M, et al. Impact of acute, oral ingestion of hypoxoside from African potato on hepatic and renal function tests in HIV infected patients on combination antiretroviral therapy. J Herb Med, 2021, 26: 100427. doi:10.1016/j.hermed.2021.100427.
[14]	马玙, N. Hiransuthikul K. E.Nelson, 等. 泰国成年HIV感染者的异烟肼预防性治疗. 结核与肺部疾病杂志, 2005, 8(2): 59-63. doi:10.3969/j.issn.1006-6942.2005.02.004.
[15]	Butov DA, Efremenko YV, Prihoda ND, et al. Randomized, placebo-controlled Phase Ⅱ trial of heat-killed Mycobacterium vaccae (Immodulon batch) formulated as an oral pill (V7). Immunotherapy, 2013, 5(10):1047-1054. doi:10.2217/imt.13.110.

指标	治疗前	治疗后		t值	P值^a	t值	P值^b
指标	治疗前	1个月	3个月	t值	P值^a	t值	P值^b
CD3⁺T细胞(个/μl,$\bar{x} \pm s$)
试验组	1221.20±399.52	1583.83±584.69	1816.67±736.86	-2.962	0.004	-4.460	<0.001
对照组	1598.31±554.44	1505.10±623.02	1716.47±689.07	0.379	0.709	-0.795	0.436
t值	-2.832	1.189	2.209
P值	0.006	0.247	0.034
CD4⁺T细胞(个/μl, $\bar{x} \pm s$)
试验组	588.71±273.44	599.10±239.56	674.10±282.30	-0.158	0.874	-2.801	0.044
对照组	499.00±216.39	481.70±268.99	559.11±187.14	0.175	0.863	-0.684	0.502
t值	1.162	0.534	3.666
P值	0.248	0.598	0.008
CD8⁺T细胞(个/μl, $\bar{x} \pm s$)
试验组	609.65±267.71	785.11±277.63	833.21±314.11	-2.392	0.135	-3.801	<0.001
对照组	998.00±491.69	826.10±383.01	1029.56±635.41	0.912	0.372	-0.131	-0.684
t值	-3.932	1.681	2.494
P值	0.000	0.106	0.006
CD4⁺/CD8⁺($\bar{x} \pm s$)
试验组	0.95±0.37	0.91±0.31	0.86±0.54	0.316	0.754	0.586	0.560
对照组	0.70±0.68	0.66±0.40	0.82±0.74	0.205	0.840	-0.378	0.710
t值	1.199	0.650	3.502
P值	0.241	0.552	0.001

母牛分枝杆菌菌苗对HIV感染合并结核分枝杆菌潜伏感染者外周血T细胞亚群的影响

Effect of Mycobacterium vaccinae on T Lymphocyte subsets in peripheral blood of HIV patients complicated with latent Mycobacterium tuberculosis infection

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 15

相关文章 15

编辑推荐

Metrics

本文评价

友情链接

指标	试验组(63例)	对照组(33例)	t值	P值
谷丙转氨酶(U/L,$\bar{x} \pm s$)	32.89±17.75	35.87±17.77	0.759	0.450
谷草转氨酶(U/L,$\bar{x} \pm s$)	27.08±9.61	27.07±8.97	-0.008	0.994
谷丙转氨酶/谷草转氨酶($\bar{x} \pm s$)	0.94±0.37	0.81±0.19	-1.893	0.062
碱性磷酸酶(U/L,$\bar{x} \pm s$)	88.01±24.26	98.93±25.14	1.960	0.054
谷氨酰胺氨基转移酶(U/L,$\bar{x} \pm s$)	49.43±26.32	50.35±34.58	0.137	0.891
总胆红素(μmol/L,$\bar{x} \pm s$)	10.75±3.18	10.30±6.20	-0.458	0.648
白蛋白(g/L,$\bar{x} \pm s$)	45.63±2.74	47.09±3.84	1.889	0.065

[1]	尚耀民, 周晓蕾, 薛运玲, 冷霞. 微卡与维生素D联合应用对初治涂阳肺结核CD4⁺ T细胞亚群平衡的影响[J]. 中国防痨杂志, 2023, 45(6): 575-582.
[2]	张沛, 赵阿会, 高敏, 甄新安, 要玉霞, 蒋建国, 孙建伟, 孙定勇. 2016—2021年河南省MTB/HIV双重感染流行特征分析[J]. 中国防痨杂志, 2023, 45(4): 377-382.
[3]	王玉香, 陈秋奇, 余鑫鑫, 詹森林, 张培泽, 邓国防. 3HP方案治疗风湿性疾病合并结核分枝杆菌潜伏感染的前瞻性研究[J]. 中国防痨杂志, 2022, 44(9): 906-910.
[4]	熊姿, 谢赐福, 宋丽新, 王孝君, 田斌, 黄竹林, 徐祖辉, 张锡兴, 白丽琼. 2011—2020年长沙市MTB/HIV双重感染流行特征分析[J]. 中国防痨杂志, 2022, 44(5): 484-488.
[5]	曹红, 邓晓岚, 钱冰, 张洁莹, 陈伟. 2014—2019年合肥市MTB/HIV双重感染防治情况分析[J]. 中国防痨杂志, 2021, 43(8): 803-807.
[6]	王丽, 熊坤龙, 朱长太, 范琳. T淋巴细胞耗竭在耐多药肺结核患者免疫表达中的初步研究[J]. 中国防痨杂志, 2021, 43(8): 808-812.
[7]	李京, 袁风顺, 李婷, 李运葵, 高文凤, 杨成彬, 何金戈, 杨文. 2013—2019年四川省凉山彝族自治州HIV/AIDS与结核病时空分布特征及相关性分析[J]. 中国防痨杂志, 2021, 43(7): 708-715.
[8]	万海方, 陶凡, 赵杰, 陈远辉, 黄焱明, 傅云斌. 老年脊柱结核患者术后发生认知功能障碍的影响因素分[J]. 中国防痨杂志, 2021, 43(5): 441-445.
[9]	刘敏, 李明俊, 余庆, 何坤, 吴玉珊, 杨红红, 李同心. 重庆市HIV与NTM双重感染患者的菌种分布及耐药情况[J]. 中国防痨杂志, 2021, 43(5): 501-505.
[10]	林静, 张晨, 董宇杰, 刘子臣, 李琨, 车南颖. HIV感染/AIDS患者感染性浅表淋巴结病的临床病理特征分析[J]. 中国防痨杂志, 2021, 43(3): 268-273.
[11]	杨妮, 苏茜, 肖月, 逯嘉, 宋杨, 饶正远, 夏岚, 何金戈, 陈闯, 张灵麟. 2158例MTB/HIV双重感染患者治疗转归及影响因素分析[J]. 中国防痨杂志, 2021, 43(3): 274-279.
[12]	李婷, 何金戈, 苏茜, 李京, 李运葵, 高文凤, 高媛, 杨文. 结核菌素试验在四川省布拖县HIV感染/AIDS患者中筛查结核感染的价值[J]. 中国防痨杂志, 2020, 42(9): 931-936.
[13]	李运葵, 何金戈, 苏茜, 李婷, 李京, 高文凤, 杨文, 毛光玉. 结核病症状筛查在四川省布拖县HIV感染/AIDS患者中发现结核病患者的价值[J]. 中国防痨杂志, 2020, 42(9): 937-941.
[14]	鲍锐, 刘晓阳, 任鹏, 张峰, 梁海燕, 王茹, 付玲, 甘地守. 脊柱结核并发HIV感染患者手术治疗特点分析[J]. 中国防痨杂志, 2020, 42(6): 645-648.
[15]	中国防痨协会骨关节结核专业分会, 中国西部骨结核联盟, 中国华北骨结核联盟, 《中国防痨杂志》编辑委员会. 脊柱结核并发HIV感染/AIDS患者诊断及治疗专家共识[J]. 中国防痨杂志, 2020, 42(5): 418-424.