基于结核病宿主免疫反应的实验室检测技术及其临床应用

doi:10.3969/j.issn.1000-6621.2021.09.006

摘要/Abstract

摘要：

结核分枝杆菌是引起人类结核病的病原体。作为胞内致病菌,结核分枝杆菌与宿主免疫系统的相互作用决定了疾病发生、发展及患者的治疗转归,因此宿主对结核分枝杆菌的免疫应答具有作为结核病早期诊断及治疗预后判断的潜在价值。特别是在目前病原学诊断技术存在诸多弊端的情况下,如何利用宿主的免疫学指标反映疾病的状态是结核病实验室诊断的重要领域。作者主要从基于结核病宿主免疫反应的临床检测技术为切入点,系统回顾了近年来本领域的基础研究热点和临床应用实例,为早期精准诊断结核病提供重要的新思路。

关键词: 结核, 宿主特异性, 免疫, 临床实验室技术

Abstract:

Mycobacterium tuberculosis is the main pathogen causing tuberculosis in humans. As an intracellular pathogen, its interaction with host immune system determines occurrence, development and outcome of the disease; host responses against M.tuberculosis have potential value in early diagnosis and prognosis of tuberculosis. In this paper, starting with detection techniques based on host immune responses, we systematically reviewed basic research hot spots and clinical application cases in order to provide important and new strategies for early, precise diagnosis of tuberculosis.

Key words: Tuberculosis, Immunity, Host specificity, Clinical laboratory techniques

逄宇, 高兴辉, 汤一苇, 高孟秋. 基于结核病宿主免疫反应的实验室检测技术及其临床应用[J]. 中国防痨杂志, 2021, 43(9): 883-892. doi: 10.3969/j.issn.1000-6621.2021.09.006

PANG Yu, GAO Xing-hui, TANG Yi-wei, GAO Meng-qiu. Host immune responses-based methods for laboratory diagnosis and clinical application of tuberculosis[J]. Chinese Journal of Antituberculosis, 2021, 43(9): 883-892. doi: 10.3969/j.issn.1000-6621.2021.09.006

图/表 4

表1

表2

儿童、免疫缺陷人群和结核病高发国家新移民人群中通过结核分枝杆菌潜伏感染检测(IGRA与TST)后进展为结核病(参考文献[30])

第一作者,年份		检测人数		IGRA和TST 试验类型		阳性结果人数		阴性结果人数		检测结果呈阳性并进展为结核病的例数	检测结果为阴性并进展为结核病的例数
儿童
Diel, 2011		104		QFT-GIT		21		83		6	0
				TST (≥5mm)		40		64		6	0
				TST (≥10mm)		40		64		4	2
Mahomed, 2011		5244		QFT-GIT		2669		2575		39	13
				TST (≥5mm)		2894		2350		40	12
Metin Timur 2014		69		QFT-GIT		0		60		0	0
				TST (≥15mm)		69		0		0	0
Noorbakhsh 2011		59		QFT-GIT		18		41		10	0
		58		TST (≥10mm)		8		50		3	7
Song, 2014		2966		QFT-GIT		317		2649		11	12
		2982		TST (≥10mm)		663		2319		13	10
				TST (≥15mm)		231		2751		133	10
免疫缺陷人群
Elzi, 2011		43		T-SPOT.TB		25		18		25	18
		44		TST (≥5mm)		22		22		22	22
第一作者,年份	检测人数		IGRA和TST 试验类型		阳性结果人数		阴性结果人数		检测结果呈阳性并进展为结核病的例数		检测结果为阴性并进展为结核病的例数
Kim, 2011	265		T-SPOT.TB		89		176		4		0
	288		TST (≥5mm)		26		262		1		3
Kim, 2015	282		QFT-GIT		7		275		0		1
	282		TST (≥5mm)		12		270		0		1
Lee, 2009	30		QFT-G		12		18		1		0
			T-SPOT.TB		15		17		0		2
			TST (≥10mm)		20		12		1		1
Lee, 2014	159		QFT-GIT		26		133		3		2
	169		TST (≥10mm)		19		150		0		5
			TST (≥15mm)		12		157		0		5
Lee, 2015	342		QFT-GIT		103		239		N/A		4
	239		TST (≥15mm)		60		179		2		2
Milman, 2014	41		QFT-G		0		41		0		0
	12		TST (≥10mm)		0		12		0		0
Moon, 2013	210		QFT-GIT		40		170		1		1
	244		TST (≥5mm)		39		205		0		2
Sester, 2014	1238		QFT-GIT		159		1079		3		5
	1217		T-SPOT.TB		193		1024		4		6
	1282		TST (≥5mm)		149		1133		4		7
Sherkat, 2014	44		T-SPOT.TB		6		38		1		0
			TST (≥10mm)		8		36		1		0
结核病高发国家的新移民
Harstad, 2010	815		QFT-GIT		238		577		8		1
			TST (≥6mm)		415		395		8		1
	813		TST (≥15mm)		121		692		3		6
Kik, 2010	327		QFT-GIT		178		149		5		3
	299		T-SPOT.TB		181		118		6		2
	339		TST (≥6mm)		288		51		9		0
	322		TST (≥15mm)		184		138		7		1

表2

表3

表4

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第一作者	培养确认数据集			所有数据集
第一作者	诊断优势比(95%CI)	异质性	假阳性率(95%CI)	诊断优势比(95%CI)	异质性	假阳性率(95%CI)
Sweeney	30.50(14.95~62.24)	0.00	0.18(0.13~0.26)	16.66(11.56~24.00)	0.00	0.20(0.16~0.24)
Kaforou	21.05(12.20~36.34)	0.00	0.23(0.16~0.33)	14.05(10.10~19.54)	0.00	0.23(0.18~0.28)
Kaforou	12.22(6.04~24.71)	0.00	0.22(0.16~0.30)	9.05(6.42~12.74)	0.00	0.22(0.17~0.29)
Anderson	4.96(2.86~8.59)	0.00	0.26(0.09~0.53)	3.91(2.90~5.26)	0.00	0.32(0.20~0.46)
Jacobsen	19.89(10.72~36.89)	4.03	0.22(0.16~0.30)	13.04(9.54~17.82)	0.00	0.21(0.17~0.26)
Kaforou	17.21(11.08~26.74)	1.13	0.25(0.17~0.34)	13.85(10.32~18.59)	0.00	0.23(0.18~0.29)
Maertzdorf	14.38(8.04~25.70)	19.07	0.27(0.21~0.34)	11.65(8.37~16.22)	0.00	0.26(0.20~0.31)
Maertzdorf	13.82(8.75~21.83)	0.73	0.24(0.18~0.31)	9.69(7.39~12.71)	3.06	0.28(0.23~0.33)
Anderson	11.26(7.50~16.92)	4.80	0.28(0.24~0.33)	10.65(7.87~14.42)	8.39	0.26(0.21~0.31)
Sambarey	19.13(10.38~35.25)	16.87	0.19(0.13~0.28)	12.18(8.54~17.37)	11.61	0.20(0.17~0.24)
DaCosta	32.44(14.90~70.63)	0.00	0.26(0.13~0.44)	13.89(8.14~23.71)	13.63	0.45(0.28~0.64)
Verhagen	1.85(1.30~2.63)	21.43	0.47(0.28~0.67)	2.90(2.03~4.15)	21.02	0.47(0.31~0.65)
Bloom	9.94(5.49~17.99)	50.55	0.21(0.13~0.32)	6.69(4.71~9.49)	23.29	0.24(0.16~0.34)
Leong	8.20(4.75~14.16)	46.33	0.27(0.18~0.39)	8.48(5.96~12.06)	23.93	0.26(0.19~0.34)
Berry	17.72(7.41~42.35)	33.39	0.16(0.09~0.27)	9.26(5.90~14.53)	25.48	0.45(0.25~0.66)
Berry	12.62(4.98~31.99)	42.89	0.19(0.04~0.57)	6.72(3.81~11.85)	27.48	0.66(0.35~0.87)

第一作者	ROC曲线下面积	患病率为2% 的阳性预测值	患病率为2% 的阴性预测值
DaCosta	0.56(0.50~0.62)	14.6	98.2
Sweeney	0.86(0.78~0.94)	13.6	99.4
Kaforou	0.86(0.78~0.94)	13.6	99.4
Kaforou	0.87(0.80~0.95)	13.2	100.0
Leong	0.73(0.62~0.83)	11.0	99.3
Jacobsen	0.85(0.76~0.93)	10.8	NC
Anderson	0.85(0.77~0.92)	8.8	99.5
Bloom	0.68(0.56~0.79)	8.3	98.9
Sambarey	0.80(0.72~0.89)	6.4	99.4
Kaforou	0.83(0.76~0.90)	6.2	99.4
Maertzdorf	0.63(0.56~0.69)	2.8	99.5
Anderson	0.46(0.34~0.58)	2.7	98.2
Maertzdorf	0.51(0.50~0.52)	2.0	99.5
Verhagen	0.47(0.45~0.49)	2.0	NC
Berry	0.50(0.50~0.50)	2.0	98.9
Berry	0.50(0.50~0.50)	2.0	NC