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Impact of donor KIRs and recipient KIR/HLA class I combinations on GVHD in patients with acute leukemia after HLA-matched sibling HSCT.
Human Immunology ( IF 3.1 ) Pub Date : 2020-03-18 , DOI: 10.1016/j.humimm.2020.03.004
Marzieh Mansouri 1 , Jean Villard 2 , Mani Ramzi 3 , Ali Alavianmehr 1 , Shirin Farjadian 1
Affiliation  

In addition to T cells, NK cells can also participate in the outcome of hematopoietic stem cell transplantation (HSCT) mainly through the interaction between donor killer cell immunoglobulin-like receptors (KIRs) and recipient human leukocyte antigen (HLA) class I molecules. There is a risk of GVHD other than leukemia relapse after allogeneic HSCT that activation of donor NK cells in the absence of appropriate inhibitory ligands will be one of the reasons. To investigate the impact of donor KIRs and recipient KIR/HLA class I combinations on GVHD and leukemia relapse in patients with acute leukemia after HSCT, 100 patients with acute leukemia who received HSCT from their HLA-matched siblings were included in this study. Genotypes of 16 KIR genes and two 2DS4 variants (full length and deleted alleles), along with HLA-A/B genotypes, were determined by PCR-SSP. HLA-C genotyping was done with the SSO-Luminex method. Chimerism analysis was done using 16 short tandem repeats (STRs) to detect early leukemia relapse. Acute (a)GVHD occurred in 38 patients, and 16 of them died during the study. None of the recipients showed any sign of leukemia relapse after HSCT. Full donor chimerism was observed in all tested patients during the first year after HSCT. Our results also indicated an increased risk of aGVHD in AA recipients with the C2/Cx, Bw4+ (or A-Bw4+) or HLA-A3/A11 genotypes who received HSCT from Bx donors. Our results showed that donor selection based on donor-recipient KIR genotypes and recipient HLA class I status can improve the outcome of HSCT.



中文翻译:

HLA匹配的同胞HSCT后,急性白血病患者中供者KIR和受体KIR / HLA I类组合对GVHD的影响。

除T细胞外,NK细胞还可以主要通过供体杀伤细胞免疫球蛋白样受体(KIR)与受体人类白细胞抗原(HLA)I类分子之间的相互作用来参与造血干细胞移植(HSCT)的结果。同种异体造血干细胞移植后,除了白血病复发外,还有发生GVHD的风险,即在缺乏适当抑制性配体的情况下激活供体NK细胞将是原因之一。为研究供体KIR和受体KIR / HLA I类组合对HSCT后急性白血病患者GVHD和白血病复发的影响,本研究纳入了100例从HLA匹配兄弟姐妹接受HSCT的急性白血病患者。16个KIR基因和2个2DS4的基因型通过PCR-SSP确定变体(全长和缺失的等位基因)以及HLA- A / B基因型。使用SSO-Luminex方法进行HLA- C基因分型。使用16个短串联重复序列(STR)进行嵌合体分析,以检测白血病的早期复发。急性(a)GVHD发生在38例患者中,其中16例在研究期间死亡。HSCT后没有任何接受者显示出白血病复发的迹象。在HSCT后的第一年内,所有接受测试的患者均观察到完全供体嵌合。我们的结果还表明,使用C2 / Cx,Bw4 +(或A-Bw4 +)或HLA- A3 -- / A11-的AA受体患aGVHD的风险增加Bx供体接受HSCT的基因型。我们的结果表明,基于供体-受体KIR基因型和受体HLA I类状态的供体选择可以改善HSCT的结果。

更新日期:2020-03-18
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