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Abstract：
Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.
摘要：
远端感觉多发性神经病（DSP）是一种致残性疾病，艾滋病毒感染者的慢性病（PWH），即使是那些抑制病毒的抗逆转录病毒治疗（ART），伴随着各种各样的并发症，比如生活质量下降。先前的研究表明，DSP与PWH中的炎症细胞因子有关。粘附分子,对正常的血管功能至关重要，在艾滋病毒和其他与DSP相关的疾病中受到干扰，但是PWH中粘附分子和DSP之间的联系尚不清楚。本研究旨在确定DSP体征和症状是否与一组炎症的血浆生物标志物相关（D-二聚体，sTNFRII,MCP-1，IL-6，IL-8，IP-10，sCD14）和血管I完整性（ICAM-1，VCAM-1，uPAR，MMP-2,VEGF,uPAR,TIMP-1，TIMP-2）和PWH和无HIV的人（PWoH）之间存在差异。通过加州大学圣地亚哥分校HIV神经行为研究计划的研究，对143名参与者（69名PWH和74名PWoH）进行了横断面研究。对所有参与者的DSP体征和症状进行临床评估。DSP被定义为两个或更多的DSP标志：双侧对称减少远端振动，尖锐的感觉，和脚踝反射。参与者报告的症状是神经性疼痛，感觉异常,和失去感觉。因子分析降低了所有参与者中15种生物标志物的维度，产生六个因素。Logistic回归用于评估生物标志物与DSP体征和症状之间的关联。控制相关的人口统计学和临床协变量。143名参与者为48.3%PWH，47名（32.9%）女性，和47（33.6％）西班牙裔，平均年龄44.3±12.9岁。在PWH中，中位数（IQR）最低点和当前CD4+T细胞分别为300（178-448）和643（502-839），分别。使用DSP的参与者年龄较大，但性别和种族分布与没有DSP的参与者相似。多因素logistic回归显示，在PWH和PWoH中，因子2（sTNFRII和VCAM-1）和因子4（MMP-2）与DSP体征独立相关（OR[95％CI]：5.45[1.42-21.00]，和15.16[1.07-215.22])，分别。这些结果表明，炎症和血管完整性改变可能有助于PWH中的DSP发病机制，但不是PWoH,可能通过内皮功能障碍和轴突变性。
