Analysis of risk factors associated with false negative results of interferon-gamma release assays on peripheral blood from tuberculosis patients

doi:10.3969/j.issn.1000-6621.2021.04.009

Abstract

Abstract:

Objective To analyse the risk factors associated with false negative results of interferon-gamma release assays (IGRA) of peripheral blood from tuberculosis patients. Methods We performed a retrospective analysis using data from tuberculosis patients at TB Department 4 of the 8th Medical Center of the Chinese People’s Liberation Army General Hospital from January 2018 to March 2020 who had peripheral blood IGRA assay results. They were divided into IGRA negative (38 patients) and IGRA positive (119 patients) groups. General information, medical history, serum biochemical indexes and peripheral T lymphocyte subpopulation data were collected. Single factor analysis and multivariate logistic regression analysis were performed to analyze risk factors associated with false negative IGRA results in tuberculosis patients. Results The M(Q₁,Q₃) of lymphocyte count, T cell count, CD4 ⁺ T cell count, CD8⁺ T cell count and NKT cell count for the negative group were 1.15 (0.77, 1.58)×10⁹ cells/L, 867.50 (508.75, 1135.50) cells/μl, 493.00 (256.00, 673.75) cells/μl, 254.50 (170.25, 429.25) cells/μl and 38.50 (16.50, 88.25) cells/μl respectively, and were significantly lower than that of the positive group: 1.46 (0.99, 1.88)×10⁹ cells/L, 1013.00 (667.00, 1394.00) cells/μl, 590.00 (386.00, 850.00) cells/μl, 335.00 (232.00, 561.00) cells/μl and 57.00 (30.00, 121.00) cells/μl (the Z values were -2.512, -2.143, -2.092, -2.303 and -2.338, and the P values were 0.012, 0.032, 0.036, 0.021 and 0.019 respectively). Logistic regression analysis indicated that patients with NKT cell counts that were lower than normal (<40 cells/μl) had a 2.440 times higher risk (95%CI: 1.159-5.134) than those with a normal NKT cell count of having a false negative IGRA result. Conclusion Lowered NKT cell counts may be a contributing factor leading to false negative peripheral blood IGRA results.

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

YU Shan, LI Zhi-ming, XU Chun-xia, WANG Tao. Analysis of risk factors associated with false negative results of interferon-gamma release assays on peripheral blood from tuberculosis patients[J]. Chinese Journal of Antituberculosis, 2021, 43(4): 346-351. doi: 10.3969/j.issn.1000-6621.2021.04.009

Figures/Tables 5

指标	β值	s $x ˉ$ 值	Wald χ²值	P值	OR(95%CI)值
NKT细胞
正常(≥40个/μl)^a					1
低于正常值(<40个/μl)	0.892	0.380	5.520	0.019	2.440(1.159~5.134)

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基本情况	IGRA假阴性组(38例)		IGRA阳性组(119例)		χ²值	P值
基本情况	例数	构成比(%)	例数	构成比(%)	χ²值	P值
性别					0.072	0.788
男	24	63.2	78	65.5
女	14	36.8	41	34.5
年龄组(岁)					0.328	0.567
<50	21	55.3	68	57.1
50~70	17	44.7	51	42.9
治疗史					0.044	0.835
初治	34	89.5	105	88.2
复治	4	10.5	14	11.8
采血前抗结核治疗时间					0.462	0.497
<4周	19	50.0	67	56.3
≥4周	19	50.0	52	43.7
基本情况	IGRA假阴性组(38例)		IGRA阳性组(119例)		χ²值	P值
基本情况	例数	构成比(%)	例数	构成比(%)	χ²值	P值
病灶部位					2.116	0.146
肺结核	22	57.9	84	70.6
肺外结核	16	42.1	35	29.4
耐药情况					0.434	0.510
是	3	7.9	6	5.0
否	35	92.1	113	95.0
糖尿病病史					0.748	0.387
是	5	13.2	23	19.3
否	33	86.8	96	80.7
吸烟史					1.121	0.290
是	9	23.7	39	32.8
否	29	76.3	80	67.2
饮酒史					2.521	0.112
是	2	5.3	18	15.1
否	36	94.7	101	84.9
结核抗体					0.301	0.583
阴性	23	60.5	66	55.5
阳性	15	39.5	53	44.5

血清生化指标	IGRA假阴性组(38例)	IGRA阳性组(119例)	Z值	P值
CA125(U/ml)	36.08(20.69,90.69)	41.50(14.80,107.90)	-0.090	0.928
ESR(mm/1h)	31.00(12.25,76.50)	33.00(15.00,67.00)	-0.199	0.842
CRP(mg/L)	34.12(10.79,71. 36)	27.35(4.09,63.70)	-1.309	0.190
淋巴细胞计数(×10⁹/L)	1.15(0.77,1.58)	1.46(0.99,1.88)	-2.512	0.012
淋巴细胞百分比(%)	21.32(12.01,27.45)	22.30(14.30,30.54)	-1.078	0.281

T细胞亚群分类	IGRA假阴性组	IGRA阳性组	Z值	P值
T细胞计数 (个/μl)	867.50(508.75,1135.50)	1013.00(667.00,1394.00)	-2.143	0.032
T细胞百分比	0.71 (0.64,0.78)	0.73(0.67,0.79)	-1.107	0.268
CD4⁺T细胞计数 (个/μl)	493.00(256.00,673.75)	590.00(386.00,850.00)	-2.092	0.036
CD4⁺T细胞百分比	0.41(0.35,0.50)	0.41(0.36,0.49)	-0.219	0.826
CD8⁺T细胞计数(个/μl)	254.50(170.25,429.25)	335.00(232.00,561.00)	-2.303	0.021
CD8⁺T细胞百分比	0.23(0.19,0.31)	0.27(0.21,0.32)	-1.492	0.136
CD4⁺/CD8⁺	1.79(1.21,2.51)	1.58(1.30,2.20)	-0.473	0.636
NK细胞计数(个/μl)	109.00(71.25,165.25)	138.00(86.00,194.00)	-1.834	0.067
NK细胞百分比	0.11(0.07,0.17)	0.09(0.06,0.16)	-1.248	0.212
NKT细胞计数(个/μl)	38.50(16.50,88.25)	57.00(30.00,121.00)	-2.338	0.019
NKT细胞百分比	0.03(0.02,0.06)	0.05(0.02,0.08)	-1.617	0.106
B细胞计数 (个/μl)	100.00(57.75,238.75)	168.00 (79.00,271.00)	-1.433	0.149
B细胞百分比	0.15(0.07,0.19)	0.13(0.08,0.17)	-0.830	0.407

变量	赋值	变量	赋值
IGRA	1=假阴性;0=阳性	CD4⁺T细胞计数(个/μl)	0=正常(≥550);1=低于正常值(<550)
淋巴细胞计数(×10⁹/L)	0=正常(≥0.8);1=低于正常值(<0.8)	CD8⁺T细胞计数(个/μl)	0=正常(≥320);1=低于正常值(<320)
T细胞计数(个/μl)	0=正常(≥966);1=低于正常值(<966)	NKT细胞计数(个/μl)	0=正常(≥40);1=低于正常值(<40)