Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection
Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection
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DOI：
10.4049/jimmunol.1302596
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发表时间：
2014-03-01
影响因子：
4.4
通讯作者：
Karlsson, Annika C.
中科院分区：
文献类型：
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作者：
Buggert, Marcus;Frederiksen, Juliet;Karlsson, Annika C.
HIV疾病进展的特征在于细胞免疫系统的许多病理变化。尽管如此，CD 4细胞计数和病毒载量代表了临床上最常用的实验室参数，以确定疾病进展。在这项研究中，我们进行了一项跨学科的研究，以确定哪些实验室参数（病毒载量，CD 4计数，CD 8计数，CD4%，CD8%，CD 4/CD 8）与免疫系统的病理变化最密切相关。采用多参数流式细胞术评估47名未经治疗的HIV感染者队列中的CD 4（+）和CD 8（+）T细胞活化（CD 38，HLA-DR）、耗竭（PD-1，Tim-3）、衰老（CD 28，CD 57）和记忆分化（CD 45 RO，CD 27）标志物。使用生物信息学方法，我们确定了139个独特的群体，代表了“联合T细胞发病机制”，这在HIV感染者和健康对照受试者之间存在显着差异。CD 38、HLA-DR和PD-1在这些独特的T细胞群中特别表达。CD 4/CD 8比值与更多病理性T细胞群相关（n = 10），平均相关系数显著高于任何其他实验室参数。我们还通过Z变换和主成分分析降低了139个独特群体的维度，这仍然确定了CD 4/CD 8比率作为联合T细胞发病机制的卓越替代物。重要的是，基线时的CD 4/CD 8比值与治疗开始后2年的CD 4恢复显著相关。这些结果表明，在未来的临床和治疗环境中，CD 4/CD 8比值将是一个合适的实验室预测指标，以监测HIV感染中的病理性T细胞事件。
HIV disease progression is characterized by numerous pathological changes of the cellular immune system. Still, the CD4 cell count and viral load represent the laboratory parameters that are most commonly used in the clinic to determine the disease progression. In this study, we conducted an interdisciplinary investigation to determine which laboratory parameters (viral load, CD4 count, CD8 count, CD4 %, CD8 %, CD4/CD8) are most strongly associated with pathological changes of the immune system. Multiparametric flow cytometry was used to assess markers of CD4(+) and CD8(+) T cell activation (CD38, HLA-DR), exhaustion (PD-1, Tim-3), senescence (CD28, CD57), and memory differentiation (CD45RO, CD27) in a cohort of 47 untreated HIV-infected individuals. Using bioinformatical methods, we identified 139 unique populations, representing the "combined T cell pathogenesis," which significantly differed between the HIV-infected individuals and healthy control subjects. CD38, HLA-DR, and PD-1 were particularly expressed within these unique T cell populations. The CD4/CD8 ratio was correlated with more pathological T cell populations (n = 10) and had a significantly higher average correlation coefficient than any other laboratory parameters. We also reduced the dimensionalities of the 139-unique populations by Z-transformations and principal component analysis, which still identified the CD4/CD8 ratio as the preeminent surrogate of combined T cell pathogenesis. Importantly, the CD4/CD8 ratio at baseline was shown to be significantly associated with CD4 recovery 2 y after therapy initiation. These results indicate that the CD4/CD8 ratio would be a suitable laboratory predictor in future clinical and therapeutic settings to monitor pathological T cell events in HIV infection.