下一代测序技术：造血干细胞移植中杀伤细胞免疫球蛋白样受体等位基因分型的新工具。
Next-generation sequencing technology a new tool for killer cell immunoglobulin-like receptor allele typing in hematopoietic stem cell transplantation.
作者信息
Maniangou B, Retière C, Gagne K
机构信息
Établissement français du sang (EFS) Pays-de-la-Loire, laboratoire de recherche, 34, boulevard Jean-Monnet, 44011 Nantes, France; Inserm U1232, CNRS, CNRS ERL, centre de recherche en cancérologie et immunologie Nantes Angers (CRCINA), équipe 1, 8, quai Moncousu, 44007 Nantes, France.
Établissement français du sang (EFS) Pays-de-la-Loire, laboratoire de recherche, 34, boulevard Jean-Monnet, 44011 Nantes, France; Inserm U1232, CNRS, CNRS ERL, centre de recherche en cancérologie et immunologie Nantes Angers (CRCINA), équipe 1, 8, quai Moncousu, 44007 Nantes, France; Établissement français du sang Pays-de-la-Loire, laboratoire HLA, 34, boulevard Jean-Monnet, 44011 Nantes cedex, France.
出版信息
Transfus Clin Biol. 2018 Feb;25(1):87-89. doi: 10.1016/j.tracli.2017.07.005. Epub 2017 Oct 12.
Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes located together within the leukocyte receptor cluster on human chromosome 19q13.4. To date, 17 KIR genes have been identified including nine inhibitory genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes vary between the individuals. In addition, these KIR genes are known to be polymorphic at allelic level (907 alleles described in July 2017). KIR genes encode for receptors which are predominantly expressed by Natural Killer (NK) cells. KIR receptors recognize HLA class I molecules and are able to kill residual recipient leukemia cells, and thus reduce the likelihood of relapse. KIR alleles of Hematopoietic Stem Cell (HSC) donor would require to be known (Alicata et al. Eur J Immunol 2016) because the KIR allele polymorphism may affect both the KIR NK cell phenotype and function (Gagne et al. Eur J Immunol 2013; Bari R, et al. Sci Rep 2016) as well as HSCT outcome (Boudreau et al. JCO 2017). The introduction of the Next Generation Sequencing (NGS) has overcome current conventional DNA sequencing method limitations, known to be time consuming. Recently, a novel NGS KIR allele typing approach of all KIR genes was developed by our team in Nantes from 30 reference DNAs (Maniangou et al. Front in Immunol 2017). This NGS KIR allele typing approach is simple, fast, reliable, specific and showed a concordance rate of 95% for centromeric and telomeric KIR genes in comparison with high-resolution KIR typing obtained to those published data using exome capture (Norman PJ et al. Am J Hum Genet 2016). This NGS KIR allele typing approach may also be used in reproduction and to better study KIR NK cell implication in the control of viral infections.
杀伤细胞免疫球蛋白样受体（KIR）基因是位于人类19号染色体q13.4上白细胞受体簇内的一组基因。迄今为止，已鉴定出17个KIR基因，包括9个抑制性基因（2DL1/L2/L3/L4/L5A/L5B、3DL1/L2/L3）、6个激活性基因（2DS1/S2/S3/S4/S5、3DS1）和2个假基因（2DP1、3DP1），它们被分为A组（KIR A）和B组（KIR B）单倍型。KIR基因的数量和性质在个体之间存在差异。此外，已知这些KIR基因在等位基因水平上具有多态性（2017年7月已描述907个等位基因）。KIR基因编码的受体主要由自然杀伤（NK）细胞表达。KIR受体识别HLA I类分子，并能够杀伤残留的受者白血病细胞，从而降低复发的可能性。造血干细胞（HSC）供体的KIR等位基因需要已知（Alicata等人，《欧洲免疫学杂志》，2016年），因为KIR等位基因多态性可能会影响KIR NK细胞的表型和功能（Gagne等人，《欧洲免疫学杂志》，2013年；Bari R等人，《科学报告》，2016年）以及造血干细胞移植的结果（Boudreau等人，《临床肿瘤学杂志》，2017年）。新一代测序（NGS）技术的引入克服了目前传统DNA测序方法耗时的局限性。最近，我们在南特的团队利用30份参考DNA开发了一种全新的对所有KIR基因进行NGS KIR等位基因分型的方法（Maniangou等人，《免疫学前沿》，2017年）。与使用外显子捕获获得的高分辨率KIR分型（Norman PJ等人，《美国人类遗传学杂志》，2016年）相比，这种NGS KIR等位基因分型方法简单、快速、可靠、特异，着丝粒和端粒KIR基因的一致性率为95%。这种NGS KIR等位基因分型方法也可用于生殖领域，并更好地研究KIR NK细胞在控制病毒感染中的作用。
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