Castley Alison, Berry Cassandra, French Martyn, Fernandez Sonia, Krueger Romano, Nolan David
Molecular and Biomedical Sciences, School of Veterinary and Life Sciences, Murdoch University, Murdoch, Perth, Western Australia, Australia; Department of Clinical Immunology, Royal Perth Hospital, Wellington Street, Perth, Western Australia, Australia.
Molecular and Biomedical Sciences, School of Veterinary and Life Sciences, Murdoch University, Murdoch, Perth, Western Australia, Australia.
PLoS One. 2014 Dec 29;9(12):e115226. doi: 10.1371/journal.pone.0115226. eCollection 2014.
We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice.
Cross-sectional evaluation of concurrent plasma and whole blood samples.
A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA.
HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001).
Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV infection.
我们研究了与HIV感染及其他慢性炎症性疾病预后效用相关的单核细胞状态的血浆和流式细胞术生物标志物，将81名具有一系列治疗结果的HIV阳性个体与21名健康对照献血者进行比较。我们的目标是开发并优化单核细胞检测方法，使其兼具生物学相关性、临床效用且易于应用于常规HIV实验室实践。
对同期血浆和全血样本进行横断面评估。
制定了一项流式细胞术方案，包括单管CD45、CD14、CD16、CD64、CD163、CD143分析及适当匹配的同型对照。通过酶联免疫吸附测定法测量可溶性CD14（sCD14）、可溶性CD163（sCD163）和CXCL10的血浆水平。
无论对HIV治疗的病毒学反应如何，HIV状态均与CD16 + 单核细胞上CD64、CD143和CD163的表达显著增加相关。与病毒血症性HIV感染相关的sCD14、sCD163和CXCL10的血浆水平也显著升高。有效的抗逆转录病毒疗法可使血浆sCD163和CXCL10水平恢复至健康对照水平，而尽管病毒学得到抑制，但sCD14水平仍保持升高（p<0.001）。
单核细胞活化的流式细胞术和血浆生物标志物表明对HIV感染存在持续的全身炎症反应，其特征为CD16 + 单核细胞表达谱的持续改变和sCD14水平升高，抗逆转录病毒疗法无法纠正这些改变，且可能具有预后意义。相比之下，抗逆转录病毒治疗后sCD163和CXCL10水平下降，表明这些生物标志物揭示了多种激活途径。将这些检测方法纳入常规临床护理是可行的，值得进一步考虑，特别是鉴于针对HIV感染中固有免疫激活的新兴治疗策略。
