Mueller Bridget R, Mehta Mitali, Campbell Maya, Neupane Niyati, Cedillo Gabriela, Lee Gina, Coyle Kaitlyn, Qi Jinging, Chen Zhihong, George Mary Catherine, Robinson-Papp Jessica
Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98 th Street, Box 1139, New York City, NY, 10029, USA.
Icahn School of Medicine at Mount Sinai, Human Immune Monitoring Center (HIMC), New York City, NY, USA.
Clin Auton Res. 2025 May 10. doi: 10.1007/s10286-025-01129-5.
Pre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unclear if ANS-immune connections delineated in these preclinical studies underlie the relationship between autonomic dysregulation and chronic inflammatory diseases in patients with human immunodeficiency virus (HIV). The aims of this study were: (1) to examine the relationship between interleukin-6 (IL-6) and the parasympathetic/vagal component of baroreflex sensitivity in people with HIV; (2) to determine whether the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; and (3) to compare the burden of non-acquired immunodeficiency syndrome (AIDS)-related co-morbidities between immunotypes.
A total of 79 adults with well-controlled HIV underwent a standard battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A, respectively) (Low: Mayo Clin Proc 68:748-752, 1993). Levels of immune biomarkers were measured in all participants using the Target 96 Inflammation Panel on the Olink proteomics platform, and immunotypes were identified using unbiased, non-negative matrix factorization. Mass cytometry (CyTOF) was completed on a subset of participants with and without autonomic neuropathy (N = 10).
Reduced BRS-V predicted higher levels of IL-6 (p = 0.002). A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy characterized by deficits in sympathetic nervous system activity (adjusted odds ratio 4.7, p = 0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities.
Deficits in the parasympathetic/cardiovagal and the sympathetic nervous system are associated with inflammation and disease burden in people living with HIV. Future longitudinal research is needed to examine causality.
临床前研究已证明自主神经系统（ANS）对免疫系统有直接影响。然而，这些临床前研究中所描述的ANS与免疫系统的联系是否构成人类免疫缺陷病毒（HIV）患者自主神经调节异常与慢性炎症性疾病之间关系的基础仍不清楚。本研究的目的是：（1）研究HIV感染者中白细胞介素-6（IL-6）与压力反射敏感性的副交感神经/迷走神经成分之间的关系；（2）确定HIV自主神经病变（AN）的亚型和严重程度是否能预测不同的免疫类型；（3）比较不同免疫类型之间非获得性免疫缺陷综合征（AIDS）相关合并症的负担。
共有79名HIV病情得到良好控制的成年人接受了一系列标准的自主神经功能测试，总结为综合自主神经严重程度评分（CASS）以及迷走神经和肾上腺素能压力反射敏感性（分别为BRS-V和BRS-A）（低：Mayo Clin Proc 68:748 - 752, 1993）。使用Olink蛋白质组学平台上的Target 96炎症检测板测量所有参与者的免疫生物标志物水平，并使用无偏、非负矩阵分解法确定免疫类型。对一部分有和没有自主神经病变的参与者（N = 10）进行了质谱流式细胞术（CyTOF）检测。
BRS-V降低预示着IL-6水平升高（p = 0.002）。由1型细胞因子（IL-6、IL-17）升高和CD8 + T细胞数量增加所定义的促炎免疫类型与以交感神经系统活动缺陷为特征的自主神经病变相关（调整后的优势比为4.7，p = 0.017）。这种促炎免疫类型的患者年龄较大，合并症负担较重。
副交感神经/心脏迷走神经和交感神经系统的缺陷与HIV感染者的炎症和疾病负担相关。未来需要进行纵向研究以检验因果关系。
