Peripheral blood expressions of PD-1，LAG-3 and related cytokines in patients with acute and chronic brucellosis

doi:10.3969/j.issn.1673-8640.2024.12.008

Abstract

Abstract:

Objective To study the changes in peripheral blood CD8⁺T cell surface programmed death receptor 1（PD-1），lymphocyte activation gene 3（LAG-3） expressions and serum interleukin-2（IL-2） and gamma-interferon（IFN-γ） levels in patients with acute and chronic brucellosis. Methods Totally，50 brucellosis patients were enrolled from the People's Hospital of Xinjiang Uygur Autonomous Region from December 2022 to August 2023，of which 25 cases were in acute stage（acute stage group） and 25 cases were in chronic stage（chronic stage group）. A total of 35 healthy subjects during the same period were enrolled as healthy control group. The clinical data and serologic determination results of all the patients were collected，and the expressions of PD-1 and LAG-3 on the surface of peripheral blood CD8⁺T cells，as well as serum IL-2 and IFN-γ levels were determined. Spearman correlation analysis was used to assess the correlation between PD-1 and LAG-3 expressions. The efficacy of each index in acute and chronic stages of brucellosis was evaluated by receiver operating characteristic（ROC） curve. Results Compared with healthy control group，the percentage of PD-1⁺CD8⁺T cells，the percentage of LAG-3⁺CD8⁺T cells，the percentage of PD-1⁺LAG-3⁺CD8⁺T cells and the levels of serum IL-2 and IFN-γ were higher in acute stage group and chronic stage group（P<0.000 1）. The percentage of PD-1⁺CD8⁺T cells and the percentage of LAG-3⁺CD8⁺T cells in chronic stage were higher than those in acute stage group（P<0.01），and the differences of PD-1⁺LAG-3⁺CD8⁺T cell percentage and serum IL-2 and IFN-γ levels between the 2 groups were not statistically significant（P>0.05）. The PD-1⁺CD8⁺T cell percentage and LAG-3⁺CD8⁺T cell percentage were positively correlated in acute and chronic stage brucellosis patients（r_s=0.591 and 0.545，P<0.01）. PD-1⁺LAG-3⁺CD8⁺T cell percentage，LAG-3⁺CD8⁺T cell percentage，PD-1⁺CD8⁺T cell percentage and IFN-γ were positively correlated with disease severity（r_s=0.726，0.425，0.368 and 0.395，P<0.05），and IL-2 did not correlate with disease severity（r_s=0.235，P=0.113）. The areas under curves（AUC） of the percentage of PD-1⁺LAG-3⁺CD8⁺T cells，the percentage of PD-1⁺CD8⁺T cells，the percentage of LAG-3⁺CD8⁺T cells，IL-2 and IFN-γ in distinguishing acute and chronic stages of brucellosis were 0.968，0.945，0.758，0.754 and 0.762，respectively. Conclusions High expressions of peripheral blood CD8⁺T cell surface inhibitory receptors（PD-1 and LAG-3） and down-regulation of pro-inflammatory factors（IL-2 and IFN-γ） in patients with chronic brucellosis suggest that patients with chronic brucellosis may undergo T-cell depletion.

Key words: Programmed death receptor 1, Lymphocyte activation gene 3, Interleukin-2, Gamma-interferon, T-cell depletion, Brucellosis

CLC Number:

R446.1

ZHU Xiaoyu, LI Zhiwei, JIA Jintong, LI Shuling, LIU Yezi, WANG Lingling, WANG Qian, LU Peipei, SHI Qinghai. Peripheral blood expressions of PD-1，LAG-3 and related cytokines in patients with acute and chronic brucellosis[J]. Laboratory Medicine, 2024, 39(12): 1173-1180.

Figures/Tables 9

References 16

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组别	例数	性别		年龄/岁	虎红平板凝集试验阳性/[例（%）]	血培养抗体试验阳性/[例（%）]	抗体滴度阳性/[例（%）]
组别	例数	男/[例（%）]	女/[例（%）]	年龄/岁	虎红平板凝集试验阳性/[例（%）]	血培养抗体试验阳性/[例（%）]	抗体滴度阳性/[例（%）]
急性期组	25	16（64.00）	9（36.00）	48.04±13.61	25（100.00）	10（40.00）	23（92.00）
慢性期组	25	18（72.00）	7（28.00）	46.65±10.92	25（100.00）	6（24.00）	25（100.00）
正常对照组	35	13（37.14）	22（62.86）	39.31±11.69
统计值		5.18		2.22	8.32	1.47	2.08
P值		0.07		0.16	0.04	0.23	0.47

组别	例数	性别		年龄/岁	虎红平板凝集试验阳性/[例（%）]	血培养抗体试验阳性/[例（%）]	抗体滴度阳性/[例（%）]
组别	例数	男/[例（%）]	女/[例（%）]	年龄/岁	虎红平板凝集试验阳性/[例（%）]	血培养抗体试验阳性/[例（%）]	抗体滴度阳性/[例（%）]
急性期组	25	16（64.00）	9（36.00）	48.04±13.61	25（100.00）	10（40.00）	23（92.00）
慢性期组	25	18（72.00）	7（28.00）	46.65±10.92	25（100.00）	6（24.00）	25（100.00）
正常对照组	35	13（37.14）	22（62.86）	39.31±11.69
统计值		5.18		2.22	8.32	1.47	2.08
P值		0.07		0.16	0.04	0.23	0.47

组别	例数	PD-1⁺CD8⁺T细胞百分比/ %	LAG-3⁺CD8⁺T细胞百分比/ %
急性期组	25	36.30 （25.70，42.80）^*#	22.65 （18.10，30.60）^*#
慢性期组	25	57.70 （51.00，61.70）^*	41.90 （35.30，52.00）^*
正常对照组	35	9.38 （5.65，14.20）	3.39 （1.43，7.43）
H值		43.60	81.90
P值		<0.000 1	<0.000 1

组别	例数	PD-1⁺CD8⁺T细胞百分比/ %	LAG-3⁺CD8⁺T细胞百分比/ %
急性期组	25	36.30 （25.70，42.80）^*#	22.65 （18.10，30.60）^*#
慢性期组	25	57.70 （51.00，61.70）^*	41.90 （35.30，52.00）^*
正常对照组	35	9.38 （5.65，14.20）	3.39 （1.43，7.43）
H值		43.60	81.90
P值		<0.000 1	<0.000 1

组别	例数	IL-2/（pg·mL^-1）	IFN-γ/（pg·mL^-1）
急性期组	25	2.84 （1.63，4.68）^**	25.04 （12.52，75.20）^*
慢性期组	25	2.44 （1.63，3.46）^**	10.83 （6.90，29.65）^*
正常对照组	35	1.12 （0.69，2.04）	5.38 （4.34，6.49）
H值		9.081	5.982
P值		<0.001	<0.01