The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2–5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman’s Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p ≤ 0.025 for each). Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV.

Graphical Abstract

中文翻译：

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自主神经病变与艾滋病毒感染者中更密集的细胞因子网络相关

自主神经系统 (ANS) 在免疫系统的调节中发挥着复杂的作用，通常通过激活免疫细胞上的 β-肾上腺素受体来产生抑制作用。我们假设 HIV 相关自主神经病变 (HIV-AN) 会导致免疫高反应性，这可以使用网络分析来描述。42 名 HIV 控制良好的成年人接受了自主神经测试，以得出综合自主神经严重程度评分 (CASS)。CASS 的观察范围为 2-5，与正常至中度 HIV-AN 一致。为了构建网络，参与者根据 CASS 被分为 4 组（即 2、3、4 或 5）。四十四个基于血液的免疫标记物作为节点包含在所有网络中，并且节点对之间的连接（即边）由它们的二元斯皮尔曼等级相关系数确定。为每个网络中的每个节点计算四个中心性度量（强度、紧密度、介数和预期影响）。每个网络中所有节点的每个中心性度量的中值被计算为网络复杂性的定量表示。四个网络的图形表示显示，随着 HIV-AN 严重程度的增加，复杂性也随之增加。网络中所有四个中心性度量的中值存在显着差异（每个 p ≤ 0.025）证实了这一点。在 HIV 感染者中，HIV-AN 与血液免疫标记物之间更强、更多的正相关性相关。二次分析的结果可用于为未来的研究生成假设，以调查 HIV-AN 作为导致 HIV 中观察到的慢性免疫激活的机制。

图形概要