Inflammatory Phenotypes Predict Changes in Arterial Stiffness Following Antiretroviral Therapy Initiation.
Inflammatory Phenotypes Predict Changes in Arterial Stiffness Following Antiretroviral Therapy Initiation.
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DOI：
10.1093/cid/ciaa186
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发表时间：
2020-12-03
期刊：
影响因子：
--
通讯作者：
Khoo S
中科院分区：
文献类型：
--
作者：
Kelly C;Tinago W;Alber D;Hunter P;Luckhurst N;Connolly J;Arrigoni F;Abner AG;Kamngona R;Sheha I;Chammudzi M;Jambo K;Mallewa J;Rapala A;Heyderman RS;Mallon PWG;Mwandumba H;Walker AS;Klein N;Khoo S
炎症驱动艾滋病毒的血管功能障碍，但在低收入环境中，炎症的原因是多方面的，包括感染和环境因素。我们假设，晚期免疫抑制患者可以分为炎症表型，这些表型可以预测ART治疗后血管功能障碍的变化。我们在REALITY试验中招募了开始ART 2周后CD 4 <100个细胞/μL的马拉维成年人（NCT 01825031）。在ART开始后2、12、24和42周测量颈动脉股动脉脉搏波速度（cfPWV）。在第2周和第42周通过电化学发光法测量血浆炎症标志物。主成分的层次聚类确定炎症簇。211名HIV受试者分为3个炎症簇，分别代表51名（24%;簇-1）、153名（73%;簇-2）和7名（3%;簇-3）个体。与簇-2和簇-3相比，簇-1显示出显著更高的HLADR和PD-1的CD 4和CD 8 T细胞表达（均P < .0001）。尽管小，但簇-3具有反映炎症（IL-6、IFN-γ、IP-10、IL-1 RA、IL-10）、趋化性（IL-8）、全身和血管炎症（CRP、ICAM-1、VCAM-1）和SAA的细胞因子的显著更高水平（均P < .001）。在混合效应模型中，簇2与簇1的cfPWV随时间的变化相似（相对倍数变化，0.99; 95% CI，0.86 -1.14; P = 0.91），但簇3与簇1的cfPWV随时间的变化更大（相对倍数变化，1.45; 95% CI，1.01-2.09; P = 0.045）。确定了两个炎性簇：一个由高T细胞PD-1表达定义，另一个由高度炎症特征和ART时cfPWV增加定义。炎症表型的进一步临床表征可以帮助将血管功能障碍干预靶向于最高风险的患者。NCT 01825031。成人开始抗逆转录病毒治疗（ART）与先进的免疫抑制可以表型分为3个炎症集群。一个簇由高T细胞PD-1表达定义，另一个簇由高度炎症的生物学特征定义。ART治疗后动脉硬度的变化因炎症表型而异。
Inflammation drives vascular dysfunction in HIV, but in low-income settings causes of inflammation are multiple, and include infectious and environmental factors. We hypothesized that patients with advanced immunosuppression could be stratified into inflammatory phenotypes that predicted changes in vascular dysfunction on ART. We recruited Malawian adults with CD4 <100 cells/μL 2 weeks after starting ART in the REALITY trial (NCT01825031). Carotid femoral pulse-wave velocity (cfPWV) measured arterial stiffness 2, 12, 24, and 42 weeks post–ART initiation. Plasma inflammation markers were measured by electrochemiluminescence at weeks 2 and 42. Hierarchical clustering on principal components identified inflammatory clusters. 211 participants with HIV grouped into 3 inflammatory clusters representing 51 (24%; cluster-1), 153 (73%; cluster-2), and 7 (3%; cluster-3) individuals. Cluster-1 showed markedly higher CD4 and CD8 T-cell expression of HLADR and PD-1 versus cluster-2 and cluster-3 (all P < .0001). Although small, cluster-3 had significantly higher levels of cytokines reflecting inflammation (IL-6, IFN-γ, IP-10, IL-1RA, IL-10), chemotaxis (IL-8), systemic and vascular inflammation (CRP, ICAM-1, VCAM-1), and SAA (all P < .001). In mixed-effects models, cfPWV changes over time were similar for cluster-2 versus cluster-1 (relative fold-change, 0.99; 95% CI, .86–1.14; P = .91), but greater in cluster-3 versus cluster-1 (relative fold-change, 1.45; 95% CI, 1.01–2.09; P = .045). Two inflammatory clusters were identified: one defined by high T-cell PD-1 expression and another by a hyperinflamed profile and increases in cfPWV on ART. Further clinical characterization of inflammatory phenotypes could help target vascular dysfunction interventions to those at highest risk. NCT01825031. Adults starting Antiretroviral Therapy (ART) with advanced immunosuppression can be phenotyped into 3 inflammatory clusters. One cluster was defined by high T-cell PD-1 expression and another by a hyperinflamed biological profile. Changes in arterial stiffness on ART varied according to inflammatory phenotype.
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DOI：
10.1097/qai.0000000000001629
发表时间：
2018-04-15
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Castillo-Mancilla JR;Morrow M;Boum Y;Byakwaga H;Haberer JE;Martin JN;Bangsberg D;Mawhinney S;Musinguzi N;Huang Y;Tracy RP;Burdo TH;Williams K;Muzzora C;Hunt PW;Siedner MJ
通讯作者：
Siedner MJ
影响因子：
6.4
作者：
Leddy, Anna M.;Roque, Annelys;Weiser, Sheri D.
通讯作者：
Weiser, Sheri D.
影响因子：
3.7
作者：
Amberbir, Alemayehu;Banda, Victor;van Oosterhout, Joep J.
通讯作者：
van Oosterhout, Joep J.
影响因子：
17.1
作者：
Bourke, Claire D.;Gough, Ethan K.;Prendergast, Andrew J.
通讯作者：
Prendergast, Andrew J.
影响因子：
3.4
作者：
Ding, Fa Ming;Li, Mengtao;Zhang, Shuyang
通讯作者：
Zhang, Shuyang