免疫特征可区分无病毒血症的HIV感染成年人。
Immunologic profiles distinguish aviremic HIV-infected adults.
作者信息
Ramirez Christina M, Sinclair Elizabeth, Epling Lorrie, Lee Sulggi A, Jain Vivek, Hsue Priscilla Y, Hatano Hiroyu, Conn Daniel, Hecht Frederick M, Martin Jeffrey N, McCune Joseph M, Deeks Steven G, Hunt Peter W
机构信息
aDepartment of Biostatistics, University of California at Los Angeles, Los AngelesbDepartment of Medicine, University of California at San Francisco, San Francisco, California, USA.
出版信息
AIDS. 2016 Jun 19;30(10):1553-62. doi: 10.1097/QAD.0000000000001049.
OBJECTIVE
Prior hypothesis-driven studies identified immunophenotypic characteristics associated with the control of HIV replication without antiretroviral therapy (HIV controllers) as well as with the degree of CD4 T-cell recovery during ART. We hypothesized that an unbiased 'discovery-based' approach might identify novel immunologic characteristics of these phenotypes.
DESIGN
We performed immunophenotyping on four 'aviremic' patient groups: HIV controllers (n = 98), antiretroviral-treated immunologic nonresponders (CD4 < 350; n = 59), antiretroviral-treated immunologic responders (CD4 > 350, n = 142), and as a control group HIV-negative adults (n = 43). We measured levels of T-cell maturation, activation, dysfunction, senescence, functionality, and proliferation.
METHODS
Supervised learning assessed the relative importance of immune parameters in predicting clinical phenotypes (controller, immunologic responder, or immunologic nonresponder). Unsupervised learning clustered immune parameters and examined if these clusters corresponded to clinical phenotypes.
RESULTS
HIV controllers were characterized by high percentages of HIV-specific T-cell responses and decreased percentages of cells expressing human leukocytic antigen-antigen D related in naive, central memory, and effector T-cell subsets. Immunologic nonresponders were characterized by higher percentages of CD4 T cells that were TNFα+ or INFγ+, higher percentages of activated naive and central memory T cells, and higher percentages of cells expressing programmed cell death protein 1. Unsupervised learning found two distinct clusters of controllers and two distinct clusters of immunologic nonresponders, perhaps suggesting different mechanisms for the clinical outcomes.
CONCLUSION
Our discovery-based approach confirmed previously reported characteristics that distinguish aviremic individuals, but also identified novel immunologic phenotypes and distinct clinical subpopulations that should lead to more focused pathogenesis studies that might identify targets for novel therapeutic interventions.
目的
先前的假设驱动研究确定了与未经抗逆转录病毒治疗的HIV复制控制（HIV控制者）以及抗逆转录病毒治疗期间CD4 T细胞恢复程度相关的免疫表型特征。我们假设一种无偏倚的“基于发现”的方法可能会识别出这些表型的新免疫特征。
设计
我们对四个“无病毒血症”患者组进行了免疫表型分析：HIV控制者（n = 98）、接受抗逆转录病毒治疗的免疫无应答者（CD4 < 350；n = 59）、接受抗逆转录病毒治疗的免疫应答者（CD4 > 350，n = 142），以及作为对照组的HIV阴性成年人（n = 43）。我们测量了T细胞成熟、激活、功能障碍、衰老、功能和增殖水平。
方法
监督学习评估免疫参数在预测临床表型（控制者、免疫应答者或免疫无应答者）中的相对重要性。无监督学习对免疫参数进行聚类，并检查这些聚类是否与临床表型相对应。
结果
HIV控制者的特征是HIV特异性T细胞反应的百分比高，以及在初始、中央记忆和效应T细胞亚群中表达人类白细胞抗原-D相关抗原的细胞百分比降低。免疫无应答者的特征是TNFα+或INFγ+的CD4 T细胞百分比更高、活化的初始和中央记忆T细胞百分比更高，以及表达程序性细胞死亡蛋白1的细胞百分比更高。无监督学习发现了控制者的两个不同聚类和免疫无应答者的两个不同聚类，这可能表明临床结果存在不同机制。
结论
我们基于发现的方法证实了先前报道的区分无病毒血症个体的特征，但也识别出了新的免疫表型和不同的临床亚群，这应该会导致更有针对性的发病机制研究，可能会识别出新治疗干预的靶点。
Zotero 插件