Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, The People's Republic of China.
Sci Rep. 2017 Aug 22;7(1):9075. doi: 10.1038/s41598-017-08699-z.
Acquired aplastic anaemia (AA) is caused by T-cells migrating to and attacking bone marrow (BM) in response to chemokines (e.g., CXCR4). We investigated CXCR4 expressions on circulating T-cell subsets, plasma IL-17A concentrations, and their correlations with AA manifestations. We enrolled 71 patients with acquired AA (36 severe AA cases [SAA] and 35 non-severe AA cases [NSAA]) and 42 healthy volunteers. We used flow cytometry and ELISA to measure circulating CD4 and CD8 T-cells, their CXCR4 expressions, and plasma IL-17A concentrations. Compared to the healthy controls, SAA patients had fewer peripheral CD4 T-cells, more CD8 T-cells, and a significantly decreased CD4/CD8 ratio which was positively correlated with AA manifestations. Patients with SAA or NSAA had higher proportions of CD4CXCR4 and CD8CXCR4 T-cells, which were negatively correlated with haemoglobin concentrations and absolute neutrophil counts. Patients with SAA or NSAA had higher plasma IL-17A concentrations, which were negatively correlated with AA manifestations and the CD4/CD8 ratio. IL-17A concentrations showed a very week correlation with CD4CXCR4 T-cells frequencies, and no correlation with CD8CXCR4 T-cells frequencies. Aberrant CXCR4 expression may allow circulating T-cells, especially CD8 T-cells, to infiltrate BM during AA progression. Elevated IL-17A concentrations may contribute to AA progression outside of the CXCR4-SDF-1α axis.
获得性再生障碍性贫血 (AA) 是由 T 细胞在趋化因子 (如 CXCR4) 的作用下迁移并攻击骨髓 (BM) 引起的。我们研究了循环 T 细胞亚群上的 CXCR4 表达、血浆 IL-17A 浓度及其与 AA 表现的相关性。我们纳入了 71 例获得性 AA 患者(36 例严重 AA 病例[SAA]和 35 例非严重 AA 病例[NSAA])和 42 名健康志愿者。我们使用流式细胞术和 ELISA 测量循环 CD4 和 CD8 T 细胞、其 CXCR4 表达和血浆 IL-17A 浓度。与健康对照组相比,SAA 患者外周血 CD4 T 细胞减少,CD8 T 细胞增多,CD4/CD8 比值显著降低,且与 AA 表现呈正相关。SAA 或 NSAA 患者的 CD4CXCR4 和 CD8CXCR4 T 细胞比例较高,与血红蛋白浓度和绝对中性粒细胞计数呈负相关。SAA 或 NSAA 患者的血浆 IL-17A 浓度较高,与 AA 表现和 CD4/CD8 比值呈负相关。IL-17A 浓度与 CD4CXCR4 T 细胞频率呈非常弱的相关性,与 CD8CXCR4 T 细胞频率无相关性。异常的 CXCR4 表达可能允许循环 T 细胞,尤其是 CD8 T 细胞,在 AA 进展过程中浸润 BM。升高的 IL-17A 浓度可能有助于 CXCR4-SDF-1α 轴之外的 AA 进展。