AIDS患者抗病毒治疗中IP-10水平的变化及临床意义

doi:10.3969/j.issn.1673-8640.2022.03.006

摘要/Abstract

摘要：

目的探讨获得性免疫缺陷综合征（AIDS）患者抗病毒治疗过程中干扰素诱生蛋白10（IP-10）水平变化及其临床意义。方法选取接受高效抗逆转录病毒治疗（HAART）的AIDS患者200例（AIDS组）,根据疗效分为HIV-1抑制组和HIV-1未抑制组,检测所有患者治疗前及治疗2周、1个月、2个月、3个月、6个月、12个月和18个月的CD4⁺T细胞百分比、CD8⁺T细胞百分比、人类免疫缺陷病毒（HIV）-1载量和IP-10水平。以健康体检者100名作为正常对照组。采用Spearman相关分析评估IP-10与其他指标之间的相关性。结果 AIDS组治疗前HIV-1 RNA水平为（4.62±0.73）lg拷贝/mL。AIDS组CD4⁺T细胞百分比显著低于正常对照组（P<0.01）,IP-10水平和CD8⁺T细胞百分比显著高于正常对照组（P<0.01）。与治疗前比较,AIDS患者随着治疗时间的延长,CD4⁺T细胞百分比逐渐升高（P<0.01）,CD8⁺T细胞百分比及IP-10、HIV-1 RNA水平逐渐降低（P<0.01）,HIV-1复制受抑制的患者比例逐渐升高（P<0.01）。治疗3、6、12和18个月时,HIV-1抑制组CD4⁺T细胞百分比均显著高于HIV-1未抑制组（P<0.01）,CD8⁺T细胞百分比和IP-10水平均低于HIV-1未抑制组（P<0.01）。Spearman相关分析结果显示,AIDS患者治疗前IP-10与CD4⁺T细胞百分比呈负相关（r=-0.763,P<0.05）,与CD8⁺T细胞百分比和HIV-1 RNA呈正相关（r值分别为0.801、0.823,P<0.05）。结论 AIDS患者IP-10水平与CD4⁺T细胞、CD8⁺T细胞及HIV-1 RNA水平有关,是潜在的AIDS病情和疗效评估的指标。

关键词: 干扰素诱生蛋白-10, 人类免疫缺陷病毒, 高效抗逆转录病毒治疗, 获得性免疫缺陷综合征

Abstract:

Objective To investigate the changes and clinical significance of interferon-inducible protein-10（IP-10） for antiviral therapy in acquired immunodeficiency syndrome（AIDS） patients. Methods Totally,200 AIDS patients（AIDS group） receiving highly active antiroviral therapy（HAART） were enrolled and classified into HIV-1 inhibition group and HIV-1 non-inhibition group according to curative effect. The percentage of CD4⁺ T cells,the percentage of CD8⁺ T cells,the virus load of human immunodeficiency virus（HIV）-1 and the level of IP-10 were determined before treatment and at 2 weeks,1 month,2 months,3 months,6 months,12 months and 18 months after treatment. A total of 100 healthy subjects were enrolled as healthy control group. Spearman correlation analysis was used to evaluate the correlation between IP-10 and the other indicators. Results The level of HIV-1 RNA in AIDS group before treatment was（4.62±0.73） lg copies/mL. The percentage of CD4⁺ T cells in AIDS group was lower than that in healthy control group（P<0.01）. The level of IP-10 and the percentage of CD8⁺ T cells were higher than those in healthy control group（P<0.01）. Compared with those before treatment,with the extension of treatment time,the percentage of CD4⁺ T cells increased gradually（P<0.01）,the percentage of CD8⁺ T cells and the levels of IP-10 and HIV-1 RNA decreased gradually（P<0.01）,and the proportion of patients with inhibited HIV-1 replication increased gradually（P<0.01）. At 3,6,12 and 18 months of treatment,the percentage of CD4⁺ T cells in HIV-1 inhibition group was higher than that in HIV-1 non-inhibition group（P<0.01）,and the percentage of CD8⁺ T cells and IP-10 level were lower than those in HIV-1 non-inhibition group（P<0.01）. Spearman correlation analysis showed that the level of IP-10 in AIDS patients was negatively correlated with the percentage of CD4⁺ T cells（r=-0.763,P<0.05）,and it was positively correlated with the percentage of CD8⁺ T cells and the level of HIV-1 RNA（r=0.801,P<0.05;r=0.823,P<0.05）. Conclusions The level of IP-10 in AIDS patients is related to the levels of CD4⁺ T cells,CD8⁺ T cells and HIV-1 RNA. It is an indicator of potential AIDS and efficacy evaluation.

Key words: Interferon-inducible protein-10, Human immunodeficiency virus, Highly active antiroviral therapy, Acquired immunodeficiency syndrome

中图分类号:

R446.1

范伟光, 苏苗苗, 孟娟, 石鹏辉, 张珍. AIDS患者抗病毒治疗中IP-10水平的变化及临床意义[J]. 检验医学, 2022, 37(3): 221-225.

FAN Weiguang, SU Miaomiao, MENG Juan, SHI Penghui, ZHANG Zhen. Changes and clinical significance of IP-10 for antiviral therapy in AIDS patients[J]. Laboratory Medicine, 2022, 37(3): 221-225.

图/表 3

参考文献 21

[1]	任其奎, 孙其玉, 田兆菊, 等. 白细胞介素-32在病毒感染性疾病中的作用研究进展[J]. 中华医院感染学杂志, 2019, 29(4):636-640.
[2]	PALSTRA R J, DE CRIGNIS E, RÖLING M D, et al. Allele-specific long-distance regulation dictates IL-32 isoform switching and mediates susceptibility to HIV-1[J]. Sci Adv, 2018, 4(2):e1701729. DOI URL
[3]	ARCHIN N M, SUNG J M, GARRIDO C, et al. Eradicating HIV-1 infection:seeking to clear a persistent pathogen[J]. Nat Rev Microbiol, 2014, 12(11):750-764. DOI URL
[4]	胡艮娣, 王晓泉, 陈祥, 等. 趋化因子IP-10在介导病毒感染性疾病中的研究进展[J]. 病毒学报, 2019, 35(4):672-678.
[5]	CERVANTES-BARRAGÁN L, FIRNER S, BECHMANN I, et al. Regulatory T cells selectively preserve immune privilege of self-antigens during viral central nervous system infection[J]. J Immunol, 2012, 188(8):3678-3685. DOI URL
[6]	SANTOS V S, GOLETTI D, KONTOGIANNI K, et al. Acute phase proteins and IP-10 as triage tests for the diagnosis of tuberculosis:systematic review and meta-analysis[J]. Clin Microbiol Infect, 2019, 25(2):169-177.
[7]	张福杰. 国家免费艾滋病抗病毒药物治疗手册[M]. 北京: 人民卫生出版社, 2012.
[8]	BROWNELL J, POLYAK S J. Molecular pathways:hepatitis C virus,CXCL10,and the inflammatory road to liver cancer[J]. Clin Cancer Res, 2013, 19(6):1347-1352. DOI URL
[9]	董海平, 刘志辉, 梁小成, 等. 血浆干扰素诱导蛋白10在不同受累范围肺结核患者血浆中的表达[J]. 南方医科大学学报, 2019, 39(5):609-613.
[10]	QIU X, XIONG T, SU X, et al. Accumulate evidence for IP-10 in diagnosing pulmonary tuberculosis[J]. BMC Infect Dis, 2019, 19(1):924. DOI URL
[11]	LEE S, CHUNG Y S, YOON C H, et al. Interferon-inducible protein 10(IP-10) is associated with viremia of early HIV-1 infection in Korean patients[J]. J Med Virol, 2015, 87(5):782-789. DOI URL
[12]	PASTOR L, CASELLAS A, RUPÉREZ M, et al. Interferon-γ-inducible protein 10(IP-10) as a screening tool to optimize human immunodeficiency virus RNA monitoring in resource-limited settings[J]. Clin Infect Dis, 2017, 65(10):1670-1675. DOI URL
[13]	PUJANTELL M, BADIA R, RAMIREZ C, et al. Long-term HIV-1 infection induces an antiviral state in primary macrophages[J]. Antiviral Res, 2016, 133:145-155. DOI URL
[14]	JIAO Y, ZHANG T, WANG R, et al. Plasma IP-10 is associated with rapid disease progression in early HIV-1 infection[J]. Viral Immunol, 2012, 25(4):333-337. DOI URL
[15]	NOEL N, LEROLLE N, LÉCUROUX C, et al. Immunologic and virologic progression in HIV controllers:the role of viral "Blips" and immune activation in the ANRS CO21 CODEX study[J]. PLoS One, 2015, 10(7):e0131922. DOI URL
[16]	ROE B, COUGHLAN S, HASSAN J, et al. Elevated serum levels of interferon-gamma-inducible protein-10 in patients coinfected with hepatitis C virus and HIV[J]. J Infect Dis, 2007, 196(7):1053-1057. DOI URL
[17]	LIOVAT A S, REY-CUILLÉ M A, LÉCUROUX C, et al. Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection[J]. PLoS One, 2012, 7(10):e46143. DOI URL
[18]	NOEL N, BOUFASSA F, LÉCUROUX C, et al. Elevated IP10 levels are associated with immune activation and low CD4⁺ T-cell counts in HIV controller patients[J]. AIDS, 2014, 28(4):467-476. DOI URL
[19]	RAMIREZ L A, ARANGO T A, THOMPSON E, et al. High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART[J]. J Leukoc Biol, 2014, 96(6):1055-1063. DOI URL
[20]	PELTENBURG N C, SCHOEMAN J C, HOU J, et al. Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy[J]. Sci Rep, 2018, 8(1):16947. DOI URL
[21]	PASTOR L, URREA V, CARRILLO J, et al. Dynamics of CD4 and CD8 T-cell subsets and inflammatory biomarkers during early and chronic HIV infection in Mozambican adults[J]. Front Immunol, 2018, 8:1925. DOI URL

组别	例数	CD4⁺T细胞/%	CD8⁺T细胞/%	IP-10/（pg/mL）
AIDS组	200	25.25±3.26	34.27±4.12	1 786.25±257.61
正常对照组	100	43.86±4.62	17.64±1.45	85.17±35.47
t值		36.005	41.496	65.669
P值		<0.001	<0.001	<0.001

组别	例数	CD4⁺T细胞/%	CD8⁺T细胞/%	IP-10/（pg/mL）
AIDS组	200	25.25±3.26	34.27±4.12	1 786.25±257.61
正常对照组	100	43.86±4.62	17.64±1.45	85.17±35.47
t值		36.005	41.496	65.669
P值		<0.001	<0.001	<0.001

时间点	CD4⁺T细胞/%	CD8⁺T细胞/%	IP-10/（pg/mL）	HIV-1 RNA/（lg拷贝/mL）	HIV-1抑制/[例（%）]
治疗前	25.25±3.26	34.57±4.12	1 786.25±257.61	4.62±0.73	0（0）
治疗后
2周	26.47±3.35^*	33.23±4.25^*	1 427.85±227.35^*	3.45±0.42^*	5（2.50）
1个月	27.82±3.41^*	32.84±3.96^*	1 294.57±196.47^*	2.94±0.37^*	16（8.00）
2个月	28.64±3.52^*	30.45±3.83^*	1 137.39±157.40^*	2.64±0.32^*	31（15.50）^*
3个月	29.12±3.63^*	29.49±3.69^*	967.39±125.67^*	2.34±0.17^*	107（53.50）^*
6个月	30.47±3.92^*	28.65±3.15^*	829.45±84.63^*	1.84±0.15^*	161（80.50）^*
12个月	31.84±4.32^*	26.14±2.75^*	653.52±47.38^*	1.12±0.11^*	185（92.50）^*
18个月	33.27±4.27^*	25.47±2.64^*	526.28±42.74^*	0.84±0.08^*	191（95.50）^*

时间点	CD4⁺T细胞/%	CD8⁺T细胞/%	IP-10/（pg/mL）	HIV-1 RNA/（lg拷贝/mL）	HIV-1抑制/[例（%）]
治疗前	25.25±3.26	34.57±4.12	1 786.25±257.61	4.62±0.73	0（0）
治疗后
2周	26.47±3.35^*	33.23±4.25^*	1 427.85±227.35^*	3.45±0.42^*	5（2.50）
1个月	27.82±3.41^*	32.84±3.96^*	1 294.57±196.47^*	2.94±0.37^*	16（8.00）
2个月	28.64±3.52^*	30.45±3.83^*	1 137.39±157.40^*	2.64±0.32^*	31（15.50）^*
3个月	29.12±3.63^*	29.49±3.69^*	967.39±125.67^*	2.34±0.17^*	107（53.50）^*
6个月	30.47±3.92^*	28.65±3.15^*	829.45±84.63^*	1.84±0.15^*	161（80.50）^*
12个月	31.84±4.32^*	26.14±2.75^*	653.52±47.38^*	1.12±0.11^*	185（92.50）^*
18个月	33.27±4.27^*	25.47±2.64^*	526.28±42.74^*	0.84±0.08^*	191（95.50）^*

时间点	例数	CD4⁺T细胞/%	CD8⁺T细胞/%	IP-10/（pg/mL）
治疗后3个月
HIV-1抑制组	107	33.35±4.15	26.57±3.17	816.98±96.54
HIV-1未抑制组	93	27.82±3.52	30.39±3.20	1 013.58±124.37
t值		9.020	7.174	9.949
P值		<0.001	<0.001	<0.001
治疗后6个月
HIV-1抑制组	161	32.72±3.96	27.13±3.22	729.14±82.35
HIV-1未抑制组	39	24.17±2.87	34.95±3.41	1 243.34±134.26
t值		12.690	13.452	30.472
P值		<0.001	<0.001	<0.001
治疗后12个月
HIV-1抑制组	185	32.37±3.75	25.53±3.13	608.01±74.36
HIV-1未抑制组	15	25.32±2.94	33.67±3.17	1 214.86±126.52
t值		7.100	9.678	28.547
P值		<0.001	<0.001	<0.001
治疗后18个月
HIV-1抑制组	191	33.68±3.42	25.18±3.15	492.97±58.64
HIV-1未抑制组	9	24.55±3.05	31.71±3.25	1 231.35±131.47
t值		7.859	6.070	34.236
P值		<0.001	<0.001	<0.001