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在接受抗逆转录病毒治疗(ART)后,HIV 感染者体内的循环(1 → 3)-β-D-葡聚糖作为免疫激活标志物下降。

Circulating (1 → 3)-β-D-Glucan as an immune activation marker decreased after ART in people living with HIV.

机构信息

Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, China.

出版信息

Front Public Health. 2022 Sep 14;10:981339. doi: 10.3389/fpubh.2022.981339. eCollection 2022.

Abstract

BACKGROUND

Plasma level of polysaccharide (1 → 3)-β-D-Glucan (βDG), as a diagnostic marker of invasive fungal infection has been reported to be elevated in people living with HIV (PLWH). We assessed the association of circulating βDG to inflammation and systemic immune activation and the effect of antiretroviral therapy (ART) on βDG in PLWH.

METHOD

Plasma and peripheral blood monocular cell samples from 120 PLWH naive to ART and after 1 year's ART were collected. Plasma levels of βDG, markers of bacterial translocation, gut damage, and cellular immune activation were quantified.

RESULT

The plasma βDG levels were negatively correlated with CD4+ T cells count ( = -0.25, = 0.005) and positively with HIV viral load ( = 0.28, = 0.002) before ART. It was also positively correlated with immune activation markers, including PD-1 expression on CD4+ T cell ( = 0.40, = 0.01) and CD8+ T cell ( = 0.47, = 0.002), as well as HLADR+CD38+ co-expression on CD8+ T cell ( = 0.56, = 0.0002), but not with the plasma levels of LPS ( = 0.02, = 0.84), LPS binding protein (LBP, = 0.11, = 0.36), soluble LPS receptor sCD14 ( = 0.04, = 0.68), intestinal fatty acid binding protein (IFABP, = -0.12, = 0.18), and regenerating islet-derived protein 3α (REG3α, = 0.18, = 0.06). After 1 year's ART, the levels of βDG were significantly decreased compared to that in pre-ART (1.31 ± 0.24 Log10 pg/ml . 1.39 ± 0.18 Log10 pg/ml, < 0.001).

CONCLUSION

The level of plasma βDG was associated with cellular immune activation and decreased after ART in PLWH, suggesting it could serve as a biomarker of immune activation and efficacy monitoring.

摘要

背景

血浆多糖(1 → 3)-β-D-葡聚糖(βDG)水平作为侵袭性真菌感染的诊断标志物,已被报道在 HIV 感染者(PLWH)中升高。我们评估了循环βDG 与炎症和全身免疫激活的关系,以及抗逆转录病毒治疗(ART)对 PLWH 中βDG 的影响。

方法

采集了 120 名未接受 ART 的 PLWH 和接受 1 年 ART 后的外周血单核细胞样本。定量检测血浆βDG、细菌易位标志物、肠道损伤和细胞免疫激活标志物。

结果

ART 前,血浆βDG 水平与 CD4+T 细胞计数呈负相关( = -0.25, = 0.005),与 HIV 病毒载量呈正相关( = 0.28, = 0.002)。它还与免疫激活标志物呈正相关,包括 CD4+T 细胞上 PD-1 表达( = 0.40, = 0.01)和 CD8+T 细胞上 PD-1 表达( = 0.47, = 0.002),以及 CD8+T 细胞上 HLADR+CD38+共表达( = 0.56, = 0.0002),但与血浆 LPS 水平( = 0.02, = 0.84)、LPS 结合蛋白(LBP, = 0.11, = 0.36)、可溶性 LPS 受体 sCD14( = 0.04, = 0.68)、肠脂肪酸结合蛋白(IFABP, = -0.12, = 0.18)和再生胰岛衍生蛋白 3α(REG3α, = 0.18, = 0.06)无关。ART 治疗 1 年后,βDG 水平与治疗前相比显著降低(1.31 ± 0.24 Log10 pg/ml 与 1.39 ± 0.18 Log10 pg/ml, < 0.001)。

结论

PLWH 中血浆βDG 水平与细胞免疫激活有关,ART 后降低,提示其可作为免疫激活和疗效监测的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870f/9516330/c2b5e6997590/fpubh-10-981339-g0001.jpg

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