Hoenigl Martin, de Oliveira Michelli Faria, Pérez-Santiago Josué, Zhang Yonglong, Morris Sheldon, McCutchan Allen J, Finkelman Malcolm, Marcotte Thomas D, Ellis Ronald J, Gianella Sara
From the Department of Medicine, Division of Infectious Diseases, University of California San Diego, San Diego, CA (MH, MFDO, JP-S, SM, SG), Department of Internal Medicine, Section of Infectious Diseases and Tropical Medicine (MH), Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria (MH), Research Laboratory, Associates of Cape Cod, Inc, Falmouth, MA (YZ, MF), Department of Psychiatry (AJM, TDM), and Department of Neurosciences, HIV Neurobehavioral Research Center, University of California, San Diego, CA (RJE).
Medicine (Baltimore). 2016 Mar;95(11):e3162. doi: 10.1097/MD.0000000000003162.
Microbial translocation from the gut is associated with immune dysfunction, persistent inflammation, and likely plays a role in the pathogenesis of neurocognitive dysfunction during HIV infection. (1→3)-β-D-Glucan (BDG) is a component of most fungal cell walls and might be a useful indicator of gut mucosal barrier impairment. The objective of this study was to evaluate whether higher blood BDG levels correlate with impaired neurocognitive functioning in a cohort of HIV-infected adults with suppressed levels of HIV RNA in blood plasma. In this cross-sectional cohort study, we measured levels of BDG in blood plasma and cerebrospinal fluid (CSF) supernatant samples in a cohort of adults with acute/early HIV infection, who initiated antiretroviral therapy (ART) during the earliest phase of infection and achieved suppressed levels of HIV RNA in blood plasma (<50 copies/mL) thereafter. We compared BDG with established biomarkers of microbial translocation, immune activation, and cognitive dysfunction (evaluated by global deficit score). We found that higher blood BDG levels were significantly related to higher global deficit scores, reflecting worse neurocognitive performance (Spearman r = 0.47; P = 0.042) among HIV-infected adults with suppressed viral loads who initiated ART early in infection. Two CSF samples presented elevated BDG levels. Interestingly, these 2 samples originated from the 2 subjects with the highest global deficit scores of the cohort. BDG may be a promising independent biomarker associated with neurocognitive functioning in virologically suppressed HIV-infected individuals.
肠道微生物易位与免疫功能障碍、持续性炎症相关,并且可能在HIV感染期间神经认知功能障碍的发病机制中起作用。(1→3)-β-D-葡聚糖(BDG)是大多数真菌细胞壁的一种成分,可能是肠道黏膜屏障受损的有用指标。本研究的目的是评估在一组血浆中HIV RNA水平受到抑制的HIV感染成人中,较高的血液BDG水平是否与神经认知功能受损相关。在这项横断面队列研究中,我们测量了一组急性/早期HIV感染成人的血浆和脑脊液(CSF)上清液样本中的BDG水平,这些成人在感染的最早阶段开始接受抗逆转录病毒治疗(ART),此后血浆中HIV RNA水平受到抑制(<50拷贝/mL)。我们将BDG与微生物易位、免疫激活和认知功能障碍的既定生物标志物(通过整体缺陷评分评估)进行了比较。我们发现,在感染早期开始接受ART且病毒载量受到抑制的HIV感染成人中,较高的血液BDG水平与较高的整体缺陷评分显著相关,这反映出神经认知表现较差(Spearman相关系数r = 0.47;P = 0.042)。两份脑脊液样本的BDG水平升高。有趣的是,这两份样本来自该队列中整体缺陷评分最高的两名受试者。BDG可能是一种有前景的独立生物标志物,与病毒学抑制的HIV感染个体的神经认知功能相关。