The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis.
The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis.
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DOI：
10.1186/s13075-018-1695-8
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发表时间：
2018-08-29
影响因子：
4.9
通讯作者：
Harper L
中科院分区：
文献类型：
--
作者：
Chanouzas D;Sagmeister M;Dyall L;Sharp P;Powley L;Johal S;Bowen J;Nightingale P;Ferro CJ;Morgan MD;Moss P;Harper L
心血管疾病是ANCA相关性血管炎（AAV）的主要死亡原因。CD 4 + CD 28 null T细胞的扩增主要见于巨细胞病毒（CMV）血清阳性个体，并与其他条件下心血管疾病风险增加有关。本研究的目的是在AAV中表型CD 4 + CD 28 null T细胞的促炎能力以及靶向和损伤内皮的能力，并研究它们与动脉僵硬度（心血管死亡率的标志物）的关系。采用流式细胞术对53例CMV血清阳性的稳定缓解的AAV患者和30例年龄匹配的CMV血清阳性的健康志愿者的CD 4 + CD 28 null T细胞进行表型分析。在未刺激的CD 4 + CD 28 null T细胞中评价内皮归巢标记物和细胞毒性分子的表达。采用颈动脉-股动脉脉搏波传导速度（PWV）测量AAV患者的动脉硬度。CD 4 + CD 28 null T细胞是CMV特异性的，表达辅助性T细胞1（Th 1）表型，具有高水平的干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）分泌。它们还共表达内皮归巢标记物CX 3 CR 1、CD 49 d和CD 11 B以及细胞毒性分子穿孔素和颗粒酶B。AAV患者和健康志愿者的CD 4 + CD 28 null T细胞表型相似，但其比例几乎是AAV患者的两倍（11.3% [3.7-19.7] vs 6.7 [2.4-8.8]; P = 0.022）。CD 4 + CD 28 null T细胞亚群的大小与AAV中PWV的增加独立相关（CD 4 + CD 28 null细胞每增加10%，PWV增加0.66 m/s，95%置信区间0.13-1.19; P = 0.016）。宿主对CMV的细胞免疫应答导致细胞毒性CD 4 + CD 28 null T细胞的扩增，这些细胞表达内皮归巢标记物，并独立地与动脉僵硬度增加（心血管死亡率的标记物）相关。抑制AAV中的CMV可能在降低心血管疾病风险方面具有治疗价值。本文的在线版本（10.1186/s13075-018-1695-8）包含补充材料，可供授权用户使用。
Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4+CD28null T cells is seen mainly in cytomegalovirus (CMV)-seropositive individuals and has been linked to increased cardiovascular disease risk in other conditions. The aims of this study were to phenotype CD4+CD28null T cells in AAV with respect to their pro-inflammatory capacity and ability to target and damage the endothelium and to investigate their relationship to arterial stiffness, a marker of cardiovascular mortality. CD4+CD28null T cells were phenotyped in 53 CMV-seropositive AAV patients in stable remission and 30 age-matched CMV-seropositive healthy volunteers by flow cytometry following stimulation with CMV lysate. The expression of endothelial homing markers and cytotoxic molecules was evaluated in unstimulated CD4+CD28null T cells. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) in patients with AAV. CD4+CD28null T cells were CMV-specific and expressed a T helper 1 (Th1) phenotype with high levels of interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) secretion. They also co-expressed the endothelial homing markers CX3CR1, CD49d and CD11b and cytotoxic molecules perforin and granzyme B. CD4+CD28null T cells were phenotypically similar in patients with AAV and healthy volunteers but their proportion was almost twice as high in patients with AAV (11.3% [3.7–19.7] versus 6.7 [2.4–8.8]; P = 0.022). The size of the CD4+CD28null T-cell subset was independently linked to increased PWV in AAV (0.66 m/s increase per 10% increase in CD4+CD28null cells, 95% confidence interval 0.13–1.19; P = 0.016). The host cellular immune response to CMV leads to the expansion of cytotoxic CD4+CD28null T cells that express endothelial homing markers and are independently linked to increased arterial stiffness, a marker of cardiovascular mortality. Suppression of CMV in AAV may be of therapeutic value in reducing the risk of cardiovascular disease. The online version of this article (10.1186/s13075-018-1695-8) contains supplementary material, which is available to authorized users.
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影响因子：
4.6
作者：
Haarala, A.;Kahonen, M.;Hurme, M.
通讯作者：
Hurme, M.
影响因子：
20.3
作者：
Bolovan-Fritts, Cynthia A.;Trout, Rodney N.;Spector, Stephen A.
通讯作者：
Spector, Stephen A.
影响因子：
14.8
作者：
Chattopadhyay, Pratip K.;Yu, Joanne;Roederer, Mario
通讯作者：
Roederer, Mario
影响因子：
27.4
作者：
Flossmann, Oliver;Berden, Annelies;Westman, Kerstin
通讯作者：
Westman, Kerstin
影响因子：
6.5
作者：
Mallat, Ziad;Taleb, Soraya;Tedgui, Alain
通讯作者：
Tedgui, Alain