杀伤细胞免疫球蛋白样受体及其同源 HLA I 类配体与伊朗患者急性髓系白血病易感性的关联

英文原题：Association of killer cell immunoglobulin-like receptors and their cognate HLA class I ligands with susceptibility to acute myeloid leukemia in Iranian patients.

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Association of killer cell immunoglobulin-like receptors and their cognate HLA class I ligands with susceptibility to acute myeloid leukemia in Iranian patients.

PubMed 2023/07/15（内容时间） Sci Rep Q1 · IF 4.9（JCR 2025）

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人群：成人技术：NK 细胞急性髓系白血病地区：其他

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中文摘要

急性髓系白血病（AML）是成人中最常见的白血病之一。在各种NK受体中，杀伤细胞免疫球蛋白样受体（KIR）通过与I类人类白细胞抗原（HLA-I）作为其配体结合，在NK细胞发育和功能中发挥不可或缺的作用。除了KIR和HLA位点的差异外，KIR/HLA-I组合对NK细胞反应有显著影响。在这项病例对照研究中，我们旨在验证KIR/HLA-I组合与伊朗西南部人群AML易感性之间的关联。采用PCR-SSP方法，使用一些新型引物对181例AML患者和181例健康对照进行KIR和HLA基因分型。

根据我们的结果，KIR3DS1（p = 0.0001，OR = 2.32，95% CI 1.51-3.58）、KIR2DS4fl（p = 0.02，OR = 1.53，95% CI 1.05-2.21）、CxT4基因型（p = 0.03，OR = 2.0，95% CI 1.05-3.82）和T4基因簇（p = 0.01，OR = 1.99，95% CI 1.17-3.41）的频率在患者中显著高于对照组，而C1/C2基因型（p = 0.00002，OR = 0.39，95% CI 0.25-0.61）、HLA-A Bw4（p = 0.02，OR = 0.6，95% CI 0.38-0.94）和HLA-A*11（p = 0.03，OR = 0.57，95% CI 0.34-0.95）等位基因在对照组中更为常见。

此外，抑制性（i）KIR/HLA-I组合分析显示，KIR2DL1( +)/HLA-C2( +)、KIR2DL2/3( +)/HLA-C1( +)、KIR3DL1( +)/HLA-A Bw4( +)和KIR3DL2( +)/HLA-A*03/11( +)在对照组中频率较高（分别为p = 0.002，OR = 0.49，95% CI 0.3-0.78；p = 0.04，OR = 0.62，95% CI 0.39-0.99；p = 0.04，OR = 0.63，95% CI 0.4-0.99；p = 0.03，OR = 0.62，95% CI 0.4-0.95）。

总体而言，对照组中iKIR/HLA-I组合的数量更多。此外，KIR3DS1(+)/HLA-B Bw4 Ile80(+)以及HLA-B Bw4/A Bw4与KIR3DS1的总和作为激活性KIR/HLA-I组合，在患者中比对照组更常见（分别为p = 0.01，OR = 1.99，95% CI 1.14-3.49和p = 0.005，OR = 1.97，95% CI 1.22-3.19）。

总之，我们的结果推测抑制性组合通过在教育过程中产生强效NK细胞，对AML发挥保护作用。值得注意的是，KIR/HLA-I组合研究可应用于血液系统恶性肿瘤同种异体NK细胞治疗的供者选择。

展开英文摘要原文

Acute myeloid leukemia (AML) is one of the most prevalent leukemia in adults. Among the various NK receptors, killer immunoglobulin-like receptors (KIRs) carry out indispensable roles in NK cell development and function through engaging with class I human leukocyte antigens (HLA-I) as their ligands. Besides divergent KIR and HLA loci, KIR/HLA-I combinations have a significant effect on NK cell response. In this case-control study, we aimed to verify the association of KIR/HLA-I combinations with susceptibility to AML in the Southwestern Iranian population.

KIR and HLA genotyping was performed with PCR-SSP by some novel primers for 181 patients with AML and 181 healthy controls. According to our results, the frequencies of KIR3DS1 (p = 0. 0001, OR = 2. 32, 95% CI 1. 51-3. 58), KIR2DS4fl (p = 0. 02, OR = 1. 53, 95% CI 1. 05-2. 21), CxT4 genotypes (p = 0. 03, OR = 2. 0, 95% CI 1. 05-3.

82), and T4 gene cluster (p = 0. 01, OR = 1. 99, 95% CI 1. 17-3. 41) were significantly higher in patients than controls, while C1/C2 genotype (p = 0. 00002, OR = 0. 39, 95% CI 0. 25-0. 61), HLA-A Bw4 (p = 0. 02, OR = 0. 6, 95% CI 0. 38-0. 94), and HLA-A*11 (p = 0. 03, OR = 0. 57, 95% CI 0. 34-0. 95) alleles were more frequent in controls.

In addition, inhibitory (i)KIR/HLA-I combinations analysis revealed higher frequencies of KIR2DL1( +)/HLA-C2( +), KIR2DL2/3( +)/HLA-C1( +), KIR3DL1( +)/HLA-A Bw4( +), and KIR3DL2( +)/HLA-A*03/11( +) in the control group (p = 0. 002, OR = 0. 49, 95% CI 0. 3-0. 78; p = 0. 04, OR = 0. 62, 95% CI 0. 39-0. 99; p = 0. 04, OR = 0. 63, 95% CI 0. 4-0. 99; and p = 0. 03, OR = 0. 62, 95% CI 0. 4-0. 95, respectively).

Overall, the number of iKIR/HLA-I combinations was more in the control group.

Moreover, KIR3DS1( +)/HLA-B Bw4 Ile80 ( +) and the sum of HLA-B Bw4/A Bw4 combined with KIR3DS1 as activating KIR/HLA-I combinations were more frequent among patients than controls (p = 0. 01, OR = 1. 99, 95% CI 1. 14-3. 49 and p = 0. 005, OR = 1. 97, 95% CI 1. 22-3. 19, respectively).

In conclusion, our results postulate that inhibitory combinations play a protective role against AML by developing potent NK cells during education. It is noteworthy that KIR/HLA-I combination studies can be applicable in donor selection for allogeneic NK cell therapy in hematological malignancies.

论文信息

作者: Mirzazadeh S、Bemani P、Halimi H、Sanaee MN、Karami N、Ramzi M、Farjadian S
第一作者单位: Department of Immunology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.Iran
通讯作者单位: Department of Immunology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran. shirinenator@gmail.com.Iran
文献类型: 非美国政府资助研究
期刊: Scientific reports2023 Jul 15

原文标识: PubMed 37454198　·　DOI 10.1038/s41598-023-38479-x

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