Effect of microcard combined with vitamin D on the balance of CD4+ T cell subsets in initially treated patients with smear positive pulmonary tuberculosis

doi:10.19982/j.issn.1000-6621.20230078

Abstract

Abstract:

Objective: To evaluate the effect of the combination of microcard (Mycobacterium vaccae vaccine) and vitamin D adjuvant therapy on the balance of CD4⁺ T cell subsets in initially treated patients with smear positive pulmonary tuberculosis (PTB), and to analyze its clinical efficacy. Methods: A prospective study was designed. According to the inclusion criteria and patient’s willing, the initially treated patients with smear positive PTB (PTB group) admitted to Henan Chest Hospital from June 2019 to June 2022 were enrolled into conventional anti-tuberculosis treatment group (control group), conventional anti-tuberculosis with microcard treatment group (microcard group) and conventional anti-tuberculosis combined with microcard and vitamin D adjuvant therapy group (combined group). Excluding those who could not complete the 6-month treatment course due to various reasons, 74 cases in each group were included (222 patients). The proportion of Th1, Th2, Th17, Treg cells and the levels of IFN-γ, IL-4, IL-17, IL-10 in peripheral blood of patients/healthy subjects were detected in each group before treatment and after 6-month treatment, and the sputum negative conversion rate, lesion and pulmonary cavities and comprehensive efficacy were evaluated by the end of 6-month treatment. Results: After six months treatment, the Th1/Th2, Treg/Th17 ratios and IFN-γ levels in the combined group (2.32±0.39, 0.45±0.03 and (16.13±2.67) pg/ml) were significantly higher than those in the microcard group (2.19±0.25, 0.34±0.03 and (14.16±3.45) pg/ml; t=2.414, P=0.017; t=22.303, P=0.000; t=3.885, P=0.000) and control group (2.08±0.37, 0.26±0.02 and (12.34±1.73) pg/ml; t=3.840, P=0.000; t=45.331, P=0.000; t=10.248, P=0.000). The levels of IL-4, IL-17 and IL-10 ((36.54±2.01) pg/ml, (27.10±3.58) pg/ml and (35.46±3.84) pg/ml) in the combined group were significantly lower than those in the microcard group ((37.23±1.78) pg/ml, (28.43±2.16) pg/ml and (43.58±4.06) pg/ml; t=2.211, P=0.029; t=2.736, P=0.007; t=12.499, P=0.000) and control group ((38.89±2.16) pg/ml, (29.40±3.27) pg/ml and (50.24±4.22) pg/ml; t=6.851, P=0.000; t=4.732, P=0.000; t=22.284, P=0.000); the negative conversion rate of sputum smear (97.30% (72/74)) and the total effective rate (91.89% (68/74)) were significantly higher than those in the microgram group (83.78% (62/74) and 79.73% (59/74); χ²=7.889, P=0.005; χ²=4.495, P=0.034) and control group (78.38% (58/74) and 77.03% (57/74); χ²=12.397, P=0.000; χ²=6.229, P=0.013). Conclusion: Conventional anti-tuberculosis combined with microcard and vitamin D adjuvant therapy can significantly promote the balance restoration of T lymphocyte subsets Th1/Th2 and Th17/Treg, and effectively improve cytokines levels of IFN-γ, IL-4, IL-17 and IL-10, and it has a significant clinical benefit.

Key words: Tuberculosis,pulmonary, Vitamin D, Tuberculosis vaccines, T lymphocyte, Interferons, Interleukin-4

CLC Number:

Shang Yaomin, Zhou Xiaolei, Xue Yunling, Leng Xia. Effect of microcard combined with vitamin D on the balance of CD4⁺ T cell subsets in initially treated patients with smear positive pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(6): 575-582. doi: 10.19982/j.issn.1000-6621.20230078

Figures/Tables 7

组别	性别[例(构成比,%)]		年龄(岁, $x ˉ$ ±s)	体质量指数 ( $x ˉ$ ±s)	吸烟[例 (构成比,%)]	饮酒[例 (构成比,%)]	胸腔积液[例 (构成比,%)]	肺空洞 (个)
组别	男性	女性	年龄(岁, $x ˉ$ ±s)	体质量指数 ( $x ˉ$ ±s)	吸烟[例 (构成比,%)]	饮酒[例 (构成比,%)]	胸腔积液[例 (构成比,%)]	肺空洞 (个)
对照组(74例)	39(52.70)	35(47.30)	41.02±2.80	21.13±1.56	27(36.49)	11(14.86)	18(24.32)	47
微卡组(74例)	36(48.65)	38(51.35)	42.01±3.51	21.56±1.33	24(32.43)	14(18.92)	17(22.97)	40
联合组(74例)	42(56.76)	32(43.24)	41.59±2.86	21.36±1.07	30(40.54)	17(22.97)	23(31.08)	42
统计检验值	χ²=0.976		F=1.937	F=1.922	χ²=1.050	χ²=1.586	χ²=1.447	-
P值	0.614		0.147	0.149	0.592	0.453	0.485	-

组别	IFN-γ (pg/ml, $x ˉ$ ±s)	IL-4 (pg/ml, $x ˉ$ ±s)	Th1/Th2 ( $x ˉ$ ±s)	IL-17 (pg/ml, $x ˉ$ ±s)	IL-10 (pg/ml, $x ˉ$ ±s)	Th17/Treg ( $x ˉ$ ±s)
健康组(222例)	32.07±5.33	21.82±3.64	2.34±0.48	10.15±1.86	22.37±2.41	0.50±0.11
PTB组(222例)	9.48±2.08	50.28±5.07	1.55±0.30	35.23±3.89	70.31±8.28	0.11±0.02
t值	58.828	67.941	20.795	86.665	82.830	51.974
P值	0.000	0.000	0.000	0.000	0.000	0.000

组别	IFN-γ(pg/ml, $x ˉ$ ±s)				IL-4(pg/ml, $x ˉ$ ±s)				Th1/Th2( $x ˉ$ ±s)
组别	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值
对照组	9.15± 2.37	12.34± 1.73	9.352	0.000	50.41± 5.07	38.89± 2.16	17.982	0.000	1.51± 0.32	2.08± 0.37	10.023	0.000
微卡组	9.68± 2.02	14.16± 3.45	9.640	0.000	50.21± 5.06	37.23± 1.78	20.816	0.000	1.55± 0.21	2.19± 0.25	12.941	0.000
联合组	9.61± 1.95	16.13± 2.67	16.964	0.000	50.22± 5.09	36.54± 2.01	21.504	0.000	1.59± 0.28	2.32± 0.39	13.080	0.000
F值	1.363	36.221			0.037	27.283			1.579	9.116
P值	0.258	0.000			0.964	0.000			0.208	0.000
t值^a	1.464	4.057			0.240	5.102			0.899	2.119
P值	0.145	0.000			0.811	0.000			0.370	0.036
t值^b	1.289	10.248			0.228	6.851			1.798	3.840
P值	0.199	0.000			0.820	0.000			0.074	0.000
t值^c	0.214	3.885			0.012	2.211			0.983	2.414
P值	0.830	0.000			0.990	0.029			0.327	0.017

组别	IL-17(pg/ml, $x ˉ$ ±s)				IL-10(pg/ml, $x ˉ$ ±s)				Th17/Treg( $x ˉ$ ±s)
组别	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值
对照组	35.17± 4.16	29.40± 3.27	9.380	0.000	71.39± 8.25	50.24± 4.22	19.634	0.000	0.10± 0.04	0.26± 0.02	30.777	0.000
微卡组	34.66± 4.34	28.43± 2.16	11.055	0.000	69.68± 6.95	43.58± 4.06	38.341	0.000	0.12± 0.08	0.34± 0.03	22.150	0.000
联合组	35.86± 3.74	27.10± 3.58	14.555	0.000	69.86± 8.29	35.46± 3.84	32.390	0.000	0.11± 0.03	0.45± 0.03	68.938	0.000
F值	1.606	10.510			1.059	248.000			2.494	918.300
P值	0.203	0.000			0.350	0.000			0.085	0.000
t值^a	0.730	2.129			1.364	9.783			1.924	19.087
P值	0.467	0.035			0.175	0.000			0.056	0.000
t值^b	1.061	4.732			1.220	22.284			1.720	45.331
P值	0.290	0.000			0.224	0.000			0.087	0.000
t值^c	1.802	2.736			0.143	12.499			1.007	22.303
P值	0.074	0.007			0.886	0.000			0.316	0.000

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组别	例数	3个月				6个月
组别	例数	阴转例数	阴转率(%)	χ²值	P值	阴转例数	阴转率(%)	χ²值	P值
对照组	74	20	27.03	1.973^a	0.160	58	78.38	0.705^a	0.401
微卡组	74	28	37.84	3.918^b	0.048	62	83.78	7.889^b	0.005
联合组	74	40	54.05	11.212^c	0.001	72	97.30	12.397^c	0.000

组别	例数	病灶[例(构成比,%)]				空洞[个(构成比,%)]
组别	例数	吸收	明显吸收	不变	恶化	总个数	闭合	缩小	不变	增大
对照组	74	23(31.08)	35(47.30)	12(16.22)	4(5.40)	47	13(27.66)	27(57.44)	6(12.77)	1(2.13)
微卡组	74	30(40.54)	32(43.24)	11(14.86)	1(1.35)	40	23(57.50)	15(37.50)	2(5.00)	0(0.00)
联合组	74	40(54.05)	28(37.84)	6(8.11)	0(0.00)	42	30(71.43)	12(28.57)	0(0.00)	0(0.00)
χ²值^a		2.902					8.699
P值		0.407					0.034
χ²值^b		11.365					19.270
P值		0.010					0.000
χ²值^c		4.166					3.211
P值		0.244					0.201

组别	例数	痊愈	显效	有效	无效	总有效
对照组	74	5(6.76)	18(24.32)	34(45.95)	17(22.97)	57(77.03)
微卡组	74	9(12.16)	21(28.38)	29(39.19)	15(20.27)	59(79.73)
联合组	74	16(21.62)	24(32.43)	28(37.84)	6(8.11)	68(91.89)
χ²值^a		1.132				0.159
P值		0.258				0.690
χ²值^b		3.438				6.229
P值		0.001				0.013
χ²值^c		2.227				4.495
P值		0.026				0.034