← 返回

联合流式细胞术 NK 细胞免疫表型分析和 KIR/HLA-C 基因分型在急性髓系白血病患者中揭示了显著差异,但提示 NK 细胞反应整体受损

英文原题:Combined flow cytometry natural killer immunophenotyping and KIR/HLA-C genotyping reveal remarkable differences in acute myeloid leukemia patients, but suggest an overall impairment of the natural killer response.

查看英文原题

Combined flow cytometry natural killer immunophenotyping and KIR/HLA-C genotyping reveal remarkable differences in acute myeloid leukemia patients, but suggest an overall impairment of the natural killer response.

PubMed 2023/03/07(内容时间) Front Med (Lausanne) Q1 · IF 3.6(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究思路按摘要原文分段

自然杀伤(NK)细胞是固有免疫中关键的抗肿瘤效应细胞。表型差异使我们能够区分三个功能成熟阶段,即未成熟、成熟和超成熟,这些阶段在受体表达、细胞因子分泌、细胞毒特性和器官归巢方面各具特征。NK细胞展现出令人印象深刻的高度多态性种系编码受体库,这些受体可以是激活性的,触发效应功能,也可以是抑制性的,限制免疫反应。在我们的研究中,我们调查了急性髓系白血病(AML)患者的外周血NK细胞。

评估了杀伤细胞免疫球蛋白样受体(KIRs)和HLA-C基因型,因为HLA-C分子是抑制性KIRs的同源抗原。

在AML中,主要抑制性KIR单倍型AA的检出比例较高,而主要活化性Bx单倍型则以2DS3频率显著偏低为特征。流式细胞术免疫表型分析显示,与健康对照相比,AML患者NK细胞总数较低,未成熟和成熟亚群百分比降低,但超成熟NK细胞明显增多。对KIR2DL1、KIR2DL2、KIR2DL3、KIR3DL1和NKG2A抑制性受体表面表达的分析揭示了显著的异质性。然而,在所有成熟亚群中均可观察到AML患者表达总体偏高的趋势。部分具有复杂核型或携带FLT3基因突变的AML患者,在NK细胞百分比或抑制性受体表达方面表现为极端离群值。

我们得出结论,尽管AML中的遗传背景研究提供了关于疾病易感性或预后的重要信息,但流式细胞术能够提供NK数量和表型方面的精细细节,这对于对这些患者进行充分的个体化评估是必要的。

展开英文摘要原文

The Killer Immunoglobulin-like receptors (KIRs) and the HLA-C genotypes were assessed, as HLA-C molecules are cognate antigens for inhibitory KIRs.

The AA mainly inhibitory KIR haplotype was found in a higher proportion in AML, while a striking low frequency of the 2DS3 characterized the mainly activating Bx haplotype. Flow cytometry immunophenotyping evidenced a lower overall count of NK cells in AML versus healthy controls, with lower percentages of the immature and mature subpopulations, but with a markedly increase of the hypermature NKs. The analysis of the KIR2DL1, KIR2DL2, KIR2DL3, KIR3DL1, and NKG2A inhibitory receptors surface expression revealed a remarkable heterogeneity. However, an overall trend for a higher expression in AML patients could be noticed in all maturation subpopulations. Some of the AML patients with complex karyotypes or displaying a FLT3 gene mutation proved to be extreme outliers in terms of NK cells percentages or inhibitory receptors expression. DISCUSSION: We conclude that while the genetic background investigation in AML offers important pieces of information regarding susceptibility to disease or prognosis, it is flow cytometry that is able to offer details of finesse in terms of NK numbers and phenotypes, necessary for an adequate individual evaluation of these patients.

论文信息

作者
Cianga VA、Rusu C、Pavel-Tanasa M、Dascalescu A、Danaila C、Harnau S、Aanei CM、Cianga P
第一作者单位
Department of Hematology, University of Medicine and Pharmacy "Grigore T. Popa", Iasi, Romania.Italy
通讯作者单位
Department of Immunology, University of Medicine and Pharmacy "Grigore T. Popa", Iasi, Romania.Italy
期刊
Frontiers in medicine2023
原文标识
PubMed 36960339 · DOI 10.3389/fmed.2023.1148748