Analysis on risk factors associated with false negative results of interferon-gamma release assay in active tuberculosis

doi:10.3969/j.issn.1000-6621.2020.12.009

Abstract

Abstract:

Objective To analysis risk factors associated with false negative result of interferon-gamma release assay (IGRA) in pulmonary tuberculosis with positive sputum smear. Methods A total of 196 pulmonary tuberculosis patients with positive sputum smear were collected from June to December 2019 in Xi’an Chest Hospital, including 145 males (74.0%) and 51 females (26.0%); the median age (M(Q₁,Q₃)) was 38 (26, 53) years. They were divided into IGRA positive group (n=106) and false negative group (n=90). Data of general information, clinical symptoms, results of laboratory test and chest CT findings were collected. Multivariate logistic regression analysis was used to analyze the risk factors associated with false negative result of IGRA in pulmonary tuberculosis patients with positive sputum smear. Results Among the 196 patients, 106 cases were IGRA positive (54.1%). The white blood cell count (M(Q₁,Q₃)) of IGRA positive group was 6.3 (5.0, 7.5)×10⁹ cells/L, which was statistically lower than that of IGRA false negative group (7.4 (5.8, 9.2)×10⁹ cells/L) (Z=-3.464, P=0.001); the erythrocyte sedimentation rate (M(Q₁,Q₃)) in IGRA positive group was also statistically lower than that in IGRA false negative group (34.5 (16.0,58.0) mm/1 h vs. 53.0 (31.8, 84.3) mm/1 h, Z=-3.492, P=0.000); however, the number of CD4⁺T lymphocytes in IGRA positive group was statistically higher than that in IGRA false negative group (553 (371,737) cells/μl vs. 432(320, 645) cells/μl, Z=-2.080, P=0.038). Using multivariate logistic regression analysis, it was showed that white blood cell count ≥7.0×10⁹ cells/L (OR(95%CI)=3.003 (1.618-5.572)), erythrocyte sedimentation rate ≥40mm/1 h (OR(95%CI)=2.270 (1.228-4.195)), CD4⁺T cell <400 cells/μl (OR(95%CI)=2.198(1.155-4.181)) were dependent risk factors for false negative result of IGRA in pulmonary tuberculosis with positive sputum smear. Conclusion The increase of white blood cell and erythrocyte sedimentation rate, as well as the decrease of CD4 ⁺T cell are dependent factors for false negative result of IGRA, the clinical application of IGRA to aid tuberculosis diagnosis should combine with other factors of patients.

Key words: Tuberculosis,pulmonary, Interferon-gamma, Immunologic tests, Risk factors, Factor analysis,statistical

MA Jin-bao, MA Ting-ting, REN Fei, YANG Han, TAN Gan-wen. Analysis on risk factors associated with false negative results of interferon-gamma release assay in active tuberculosis[J]. Chinese Journal of Antituberculosis, 2020, 42(12): 1299-1304. doi: 10.3969/j.issn.1000-6621.2020.12.009

Figures/Tables 3

因素	IGRA阳性组 (106例)	IGRA假阴性组 (90例)	统计检验值	P值
性别[例(构成比,%)]			χ²=3.133	0.077
男	73(68.9)	72(80.0)
女	33(31.1)	18(20.0)
年龄[例(构成比,%)]			χ²=2.794	0.247
17~岁	60(56.6)	42(46.7)
40~岁	32(30.2)	29(32.2)
≥60岁	14(13.2)	19(21.1)
卡介苗接种史[例(构成比,%)]			χ²=1.371	0.242
是	71(67.0)	53(58.9)
否	35(33.0)	37(41.1)
结核病患者类型[例(构成比,%)]			χ²=0.117	0.732
初治	80(75.5)	66(73.3)
复治	26(24.5)	24(26.7)
并发糖尿病[例(构成比,%)]			χ²=0.014	0.906
是	17(16.0)	15(16.7)
否	89(84.0)	75(83.3)
结核病程[例(构成比,%)]			χ²=0.203	0.652
<8周	65(61.3)	58(64.4)
≥8周	41(38.7)	32(35.6)
痰菌[例(构成比,%)]			χ²=3.847	0.278
+	61(57.5)	59(65.6)
++	23(21.7)	12(13.3)
+++	11(10.4)	6(6.7)
++++	11(10.4)	13(14.4)
对一线抗结核药品耐药[例(构成比,%)]			χ²=0.019	0.889
是	32(30.2)	28(31.1)
否	74(69.8)	62(68.9)
BMI[M(Q₁,Q₃)]	19.8(17.6,22.3)	19.0(16.6,20.8)	Z=-2.423	0.015
发热[例(发生率,%)]	35(33.0)	41(45.6)	χ²=3.222	0.073
咳嗽[例(发生率,%)]	90(84.9)	79(87.8)	χ²=0.338	0.561
咳痰[例(发生率,%)]	85(80.2)	74(82.2)	χ²=0.131	0.717
体质量减轻[例(发生率,%)]	30(28.3)	37(41.1)	χ²=3.550	0.060
白细胞计数[×10⁹个/L,M(Q₁,Q₃)]	6.3(5.0,7.5)	7.4(5.8,9.2)	Z=-3.464	0.001
中性粒细胞百分比( $x ˉ$ ±s)	0.71±0.09	0.75±0.09	t=-2.802	0.006
淋巴细胞百分比[M(Q₁,Q₃)]	0.21(0.15,0.26)	0.16(0.11,0.22)	Z=-3.528	0.000
血红蛋白(g/L, $x ˉ$ ±s)	122.7±19.7	113.8±21.7	t=2.986	0.003
血小板计数[×10⁹个/L,M(Q₁,Q₃)]	258(191,320)	285(193,399)	Z=-2.095	0.036
血清总蛋白[g/L,M(Q₁,Q₃)]	67.1(62.2,70.6)	67.2(62.3,71.4)	Z=-0.087	0.931
血清白蛋白[g/L,M(Q₁,Q₃)]	38.9(35.2,41.7)	37.1(31.9,39.7)	Z=-2.747	0.006
血腺苷脱氨酶 [U/L,M(Q₁,Q₃)]	12.0(9.8,16.0)	13.0(10.0,18.0)	Z=-1.520	0.129
血红细胞沉降率[mm/1h,M(Q₁,Q₃)]	34.5(16.0,58.0)	53.0(31.8,84.3)	Z=-3.492	0.000
C反应蛋白[mg/L,M(Q₁,Q₃)]	30.3(8.3,68.9)	60.3(29.9,103.0)	Z=-3.899	0.000
总T淋巴细胞计数[个/μl,M(Q₁,Q₃)]	918(655,1297)	784(590,1073)	Z=-1.951	0.051
CD4⁺T淋巴细胞计数[个/μl,M(Q₁,Q₃)]	553(371,737)	432(320,645)	Z=-2.080	0.038
CD8⁺T淋巴细胞计数[个/μl,M(Q₁,Q₃)]	345(225,503)	317(219,485)	Z=-0.804	0.422
CD4⁺/CD8⁺比值[M(Q₁,Q₃)]	1.5(1.1,1.9)	1.4(1.0,1.8)	Z=-1.101	0.271
病灶累及肺野数[例(构成比,%)]			χ²=2.168	0.141
<4个肺野	45(42.5)	29(32.2)
≥4个肺野	61(57.5)	61(67.8)
肺部空洞数[例(构成比,%)]			χ²=0.636	0.425
<2个空洞	46(43.4)	34(37.8)
≥2个空洞	60(56.6)	56(62.2)

变量	β值	s $x ˉ$ 值	Wald χ²值	OR(95%CI)值	P值
白细胞计数≥7.0×10⁹个/L	1.099	0.315	12.144	3.003(1.618~5.572)	0.000
血红细胞沉降率≥40mm/1h	0.820	0.313	6.844	2.270(1.228~4.195)	0.009
CD4⁺T淋巴细胞计数<400 个/μl	0.787	0.328	5.762	2.198(1.155~4.181)	0.016

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变量	赋值	变量	赋值
BMI	0=<19.5;1=≥19.5	血小板计数(×10⁹个/L)	0=<300;1=≥300
白细胞计数(×10⁹个/L)	0=<7.0;1=≥7.0	血清白蛋白(g/L)	0=<35;1=≥35
中性粒细胞百分比(%)	0=<70;1=≥70	血红细胞沉降率(mm/1h)	0=<40;1=≥40
淋巴细胞百分比(%)	0=<20;1=≥20	C反应蛋白(mg/L)	0=<50;1=≥50
血红蛋白(g/L)	0=<120;1=≥120	CD4⁺T淋巴细胞计数(个/μl)	0=≥400;1=<400