Chronic Kidney Disease Severity Is Associated With Selective Expansion of a Distinctive Intermediate Monocyte Subpopulation
Chronic Kidney Disease Severity Is Associated With Selective Expansion of a Distinctive Intermediate Monocyte Subpopulation
复制标题
慢性肾病的严重程度与独特的中间单核细胞亚群的选择性扩增有关
作者：
S. Naicker;S. Cormican;Tomás P. Griffin;Tomás P. Griffin;Silvia Maretto;W. P. Martin;J. Ferguson;Deirdre Cotter;Eanna P Connaughton;M. Dennedy;M. Griffin
慢性肾脏疾病（CKD）影响了世界11-13%的人口，并大大增加了动脉粥样硬化性心血管疾病（ASCVD）和死亡的风险。它的特点是全身性炎症和血液白细胞的紊乱，目前尚不完全清楚。特别是，在CKD和终末期肾脏疾病中，三种主要单核细胞亚群（经典、中间和非经典）的数量和相对比例异常被描述。在这项研究中，我们描述了肾功能从正常到晚期CKD的成人血液白细胞亚型的绝对数量。主要目的是确定与当前估计的肾小球滤过率（eGFR）和随后的eGFR下降率最密切相关的单核细胞亚群。采用多色流式细胞术对成人1-5期CKD患者（154例）和健康成人（33例）的全血和外周血单核细胞（PBMC）样本进行白细胞和单核细胞群计数。进行多元线性回归分析，以确定白细胞和单核细胞数量与临床特征之间的关系，包括eGFR和eGFR下降率，并调整年龄和性别。在全血中，患有CKD 1-5的成年人的总单核细胞和中性粒细胞（而不是淋巴细胞）数量比没有CKD的人高，并且即使在年龄校正后也与当前的eGFR显著相关。在PBMC中，CKD 1-5中经典和中间单核细胞数量较高，但在年龄校正分析中，只有中间单核细胞数量与当前eGFR显著相关。当中间单核细胞进一步细分为ⅱ类MHC中高表达的单核细胞（HLA-DRmid和HLA-DRhi中间单核细胞）时，发现在CKD 1-5中，与无CKD相比，只有DRhi中间单核细胞的数量增加，并且在总的（no CKD + CKD 1-5）研究队列以及已确诊CKD（仅CKD 1-5）研究队列中，与eGFR显著相关，与年龄无关。此外，血液中DRhi中间单核细胞的数量被证明与随后的肾功能下降率显著相关。总之，我们的数据证实了CKD中中性粒细胞和单核细胞亚群失调，并确定了与肾功能丧失率较高相关的中间单核细胞的独特亚群。
Chronic kidney disease (CKD) affects 11–13% of the world's population and greatly increases risk of atherosclerotic cardiovascular disease (ASCVD) and death. It is characterized by systemic inflammation and disturbances in the blood leukocytes that remain incompletely understood. In particular, abnormalities in the numbers and relative proportions of the three major monocyte subsets—classical, intermediate, and non-classical—are described in CKD and end-stage renal disease. In this study, we characterized absolute numbers of blood leukocyte subtypes in adults with renal function varying from normal to advanced CKD. The primary aim was to identify monocyte subpopulations that associated most closely with current estimated glomerular filtration rate (eGFR) and subsequent rate of eGFR decline. Leucocyte and monocyte populations were enumerated by multi-color flow cytometry of whole blood and peripheral blood mononuclear cell (PBMC) samples from adults with CKD stage 1–5 (n = 154) and healthy adults (n = 33). Multiple-linear regression analyses were performed to identify associations between numbers of leucocyte and monocyte populations and clinical characteristics including eGFR and rate of eGFR decline with adjustment for age and gender. In whole blood, total monocyte and neutrophil, but not lymphocyte, numbers were higher in adults with CKD 1-5 compared to no CKD and were significantly associated with current eGFR even following correction for age. In PBMC, classical and intermediate monocyte numbers were higher in CKD 1-5 but only intermediate monocyte numbers were significantly associated with current eGFR in an age-corrected analysis. When intermediate monocytes were further sub-divided into those with mid- and high-level expression of class II MHC (HLA-DRmid and HLA-DRhi intermediate monocytes) it was found that only DRhi intermediate monocytes were increased in number in CKD 1-5 compared to no CKD and were significantly associated with eGFR independently of age among the total (No CKD + CKD 1-5) study cohort as well as those with established CKD (CKD 1-5 only). Furthermore, blood number of DRhi intermediate monocytes alone proved to be significantly associated with subsequent rate of renal functional decline. Together, our data confirm neutrophil and monocyte subset dysregulation in CKD and identify a distinct subpopulation of intermediate monocytes that is associated with higher rate of loss of kidney function.
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影响因子：
19.6
作者：
van der Velde, Marije;Matsushita, Kunihiro;Gansevoort, Ron T.
通讯作者：
Gansevoort, Ron T.
影响因子：
19.6
作者：
Lee, Soo Bong;Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
20.3
作者：
Ziegler-Heitbrock, Loems;Ancuta, Petronela;Lutz, Manfred B.
通讯作者：
Lutz, Manfred B.
影响因子：
5
作者：
Lee, CD;Folsom, AR;Wolfe, DA
通讯作者：
Wolfe, DA
影响因子：
29.7
作者：
Galkina E;Ley K
通讯作者：
Ley K