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肝硬化患者脾切除术后的免疫后果。

Immunological consequences following splenectomy in patients with liver cirrhosis.

作者信息

Hirakawa Yusuke, Ogata Toshiro, Sasada Tetsuro, Yamashita Takuto, Itoh Kyogo, Tanaka Hiroyuki, Okuda Koji

机构信息

Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Department of Surgery, St. Mary's Hospital, Kurume, Fukuoka 830-8543, Japan.

出版信息

Exp Ther Med. 2019 Jul;18(1):848-856. doi: 10.3892/etm.2019.7640. Epub 2019 Jun 3.

Abstract

The immune status in patients with liver cirrhosis is generally impaired due to concomitant hypersplenism. As the spleen is the largest lymphoid organ, deleterious events resulting from splenectomy are of concern in these patients. However, the immunological consequences after splenectomy have not yet been fully elucidated. In the present study, the immune status after splenectomy was comprehensively examined. Splenectomy was performed in 11 patients with liver cirrhosis and hypersplenism, and the immune status in peripheral blood was examined and compared before and at 1, 3 and 6 months after splenectomy. Splenectomy significantly lowered the neutrophil-to-lymphocyte ratio, due to a surge in lymphocytes in the peripheral circulation at 3 and 6 months after splenectomy. The frequency of cluster of differentiation (CD)4 T cells decreased after splenectomy, whereas the frequency of CD8 T cells increased. Notably, the frequencies of the naïve and central memory subsets of CD4 and CD8 T cells decreased, whereas those of the effector memory subset trended upward. In addition, the frequencies of other immune cells such as γδ T cells, natural killer T cells and natural killer cells transiently increased, while inhibitory cells such as regulatory T cells and myeloid-derived suppressor cells significantly decreased. T-cell responses to viral- and tumor-associated antigens increased after splenectomy in five of eight and two of five patients, respectively. To the best of our knowledge, this is the first study to precisely examine the drastic changes of immunological phenotypes in peripheral blood after splenectomy in patients with cirrhosis. Our findings suggested that splenectomy in patients with cirrhosis may ameliorate the impaired immune status, possibly by reducing suppressive cells and enhancing the effector cell population and function, which could, at least in part, explain the mechanisms responsible for the clinical benefits of splenectomy.

摘要

由于合并脾功能亢进,肝硬化患者的免疫状态通常受损。脾脏是最大的淋巴器官,脾切除术后产生的有害事件在这些患者中备受关注。然而,脾切除术后的免疫后果尚未完全阐明。在本研究中,对脾切除术后的免疫状态进行了全面检查。对11例肝硬化合并脾功能亢进患者进行了脾切除术,并在脾切除术前以及术后1、3和6个月对外周血免疫状态进行了检查和比较。脾切除术后中性粒细胞与淋巴细胞比值显著降低,这是由于脾切除术后3个月和6个月外周循环中淋巴细胞激增所致。脾切除术后分化簇(CD)4 T细胞频率降低,而CD8 T细胞频率增加。值得注意的是,CD4和CD8 T细胞的初始和中央记忆亚群频率降低,而效应记忆亚群频率呈上升趋势。此外,γδ T细胞、自然杀伤T细胞和自然杀伤细胞等其他免疫细胞的频率短暂增加,而调节性T细胞和髓源性抑制细胞等抑制性细胞显著减少。脾切除术后,分别有八分之五的患者对病毒相关抗原和五分之二的患者对肿瘤相关抗原的T细胞反应增强。据我们所知,这是第一项精确研究肝硬化患者脾切除术后外周血免疫表型剧烈变化的研究。我们的研究结果表明,肝硬化患者的脾切除术可能通过减少抑制性细胞、增强效应细胞群体及其功能来改善受损的免疫状态,这至少可以部分解释脾切除术临床获益的机制。

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