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揭示HIV免疫无应答者的神经免疫学特征:一种多模态MRI方法。

Unveiling neuroimmunology profile of immunological non-responders in HIV: a multimodal MRI approach.

作者信息

Zhang Yang, Ji Jiahao, Zheng Luyao, Cai Miaotian, Sun Guangqiang, Ma Yundong, Zhang Xin, Chen Xue, Zhang Yulin, Lin Xiao, Li Zhen, Zhang Tong

机构信息

Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.

Beijing Key Laboratory of HIV/AIDS Research, Beijing, China.

出版信息

Front Immunol. 2024 Dec 13;15:1452532. doi: 10.3389/fimmu.2024.1452532. eCollection 2024.

Abstract

BACKGROUND

People living with HIV (PLWH), especially immunological non-responders (INRs), may experience adverse neurologic events. However, the extent of neurological impairment in INRs remains uncertain. This study evaluates brain structure and function, immune dysregulation, and peripheral immunomarkers in INRs and immunological responders (IRs) among PLWH, classified according to immunological response criteria, within a clinical research setting.

METHODS

This study utilized multi-modal MRI to assess brain structure and function in INRs (n = 25) and IRs (n = 53). Mass cytometry and Luminex/ELISA assays were employed to analyze peripheral blood monocytes, T cell subpopulations, cytokines, chemokines, neurotrophic factors, and endocrine factors.

RESULTS

Neuroimaging findings revealed notable changes in brain structure and function in INRs, including increased fractional amplitude of low-frequency fluctuations and regional homogeneity in the left middle temporal gyrus, as well as decreased grey matter volume in the left middle temporal gyrus, left lingual gyrus, and right rolandic operculum. Furthermore, INRs exhibited significant alterations in functional connectivity in the temporal and occipital gyrus. Mass cytometry analysis demonstrated significant immune dysregulation in INRs, characterised by increased levels of senescent and activated T cells, and heightened monocyte activation. Additionally, noteworthy associations were found between neurological abnormalities and peripheral levels of immunomarkers, inflammatory cytokines, chemokines, neurotrophic factors, and endocrine factors in INRs.

CONCLUSION

These findings underscore the associations between immune dysfunction and changes in brain structure and function, emphasizing the importance of further investigations in this field.

摘要

背景

人类免疫缺陷病毒感染者(PLWH),尤其是免疫无应答者(INR),可能会经历不良神经事件。然而,INR中神经功能障碍的程度仍不确定。本研究在临床研究环境中,根据免疫应答标准,评估PLWH中INR和免疫应答者(IR)的脑结构和功能、免疫失调及外周免疫标志物。

方法

本研究利用多模态磁共振成像评估25例INR和53例IR的脑结构和功能。采用质谱流式细胞术和Luminex/酶联免疫吸附测定法分析外周血单核细胞、T细胞亚群、细胞因子、趋化因子、神经营养因子和内分泌因子。

结果

神经影像学结果显示INR的脑结构和功能有显著变化,包括左侧颞中回低频波动分数振幅增加和区域均一性增加,以及左侧颞中回、左侧舌回和右侧中央 operculum灰质体积减少。此外,INR在颞叶和枕叶的功能连接也有显著改变。质谱流式细胞术分析表明INR存在显著的免疫失调,其特征为衰老和活化T细胞水平增加以及单核细胞活化增强。此外,还发现INR的神经异常与外周免疫标志物、炎性细胞因子、趋化因子、神经营养因子和内分泌因子水平之间存在显著关联。

结论

这些发现强调了免疫功能障碍与脑结构和功能变化之间的关联,凸显了该领域进一步研究的重要性。

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