CSF/plasma HIV-1 RNA discordance even at low levels is associated with up-regulation of host inflammatory mediators in CSF

被引：22

作者：

Nightingale, Sam ^{[1
,2
,3
]}

Michael, Benedict D. ^{[1
,4
]}

Fisher, Martin ^{[5
]}

Winston, Alan ^{[6
]}

Nelson, Mark ^{[7
]}

Taylor, Steven ^{[8
]}

Ustianowski, Andrew ^{[9
]}

Ainsworth, Jonathan ^{[10
]}

Gilson, Richard ^{[11
]}

Haddow, Lewis ^{[11
]}

Ong, Edmund ^{[12
]}

Leen, Clifford ^{[13
]}

Minton, Jane ^{[14
]}

Post, Frank ^{[15
]}

Beloukas, Apostolos ^{[1
]}

Borrow, Ray ^{[16
]}

Pirmohamed, Munir ^{[2
]}

Geretti, Anna Maria ^{[1
]}

Khoo, Saye ^{[2
]}

Solomon, Tom ^{[1
,4
]}

机构：

[1] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, England

[2] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool L69 3BX, Merseyside, England

[3] Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Liverpool, Merseyside, England

[4] Walton Ctr Neurol & Neurosurg, Liverpool, Merseyside, England

[5] Brighton & Sussex Univ Hosp NHS Trust, Brighton, E Sussex, England

[6] Imperial Coll Heathcare NHS Trust, St Marys Hosp, London, England

[7] St Stephens AIDS Res Trust & Chelsea & Westminste, London, England

[8] Heart England NHS Fdn Trust, Birmingham Heartlands Hosp, Crumpsall, England

[9] Pennine Acute Hosp NHS Trust, North Manchester Gen Hosp, Crumpsall, England

[10] North Middlesex Univ Hosp NHS Trust, London, England

[11] UCL, Res Dept Infect & Populat Hlth, London WC1E 6BT, England

[12] Newcastle Upon Tyne Hosp NHS Trust, Royal Victoria Infirm, Newcastle Upon Tyne, Tyne & Wear, England

[13] NHS Lothian, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland

[14] Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Leeds, W Yorkshire, England

[15] Kings Coll Hosp NHS Fdn Trust, London, England

[16] HPA North West, Vaccine Evaluat Unit, Manchester, Lancs, England

来源：

CYTOKINE | 2016年 / 83卷

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HIV; Cerebrospinal fluid; CSF escape; Sanctuary site; Inflammation; IMMUNODEFICIENCY-VIRUS INFECTION; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; NEUROCOGNITIVE DISORDERS; ANTIRETROVIRAL THERAPY; IMPAIRMENT; BIOMARKERS; MARKERS; PLASMA; ERA;

D O I：

10.1016/j.cyto.2016.04.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Introduction: HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines, chemokines and associated mediators were raised in patients with CSF/plasma discordance at different levels. Methods: A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples matched for plasma HIV-1 RNA. Discordant samples were subdivided into 'high discordance' (>1log(10)) and low discordance' (0.5-1log(10), or ultrasensitive discordance). CSF mediators significant in univariate analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative mediator concentrations. Results: In univariate analysis 19 of 21 CSF mediators were significantly higher in discordant than non discordant samples. There were no significant differences between samples with high versus low discordance. The samples grouped into two clusters which corresponded to CSF/plasma discordance (p < 0.0001). In cluster one all mediators had relatively high abundance; this included 18 discordant samples and three non-discordant samples. In cluster two all mediators had relatively low abundance; this included 18 non-discordant samples and one non-discordant sample with ultrasensitive discordance only. Conclusions: CSF/plasma discordance is associated with potentially damaging neuroinflammatory process. Patients with discordance at lower levels (ie. 0.5-1log(10)) should also be investigated as mediator profiles were similar to those with discordance >1log(10). Sensitive testing may have a role to determine whether ultrasensitive discordance is present in those with low level CSF escape. (C) 2016 Published by Elsevier Ltd.

引用

页码：139 / 146

页数：8

共 27 条

[1] Assessment, Diagnosis, and Treatment of HIV-Associated Neurocognitive Disorder: A Consensus Report of the Mind Exchange Program [J].