Scquizzato Elisa, Zambello Renato, Teramo Antonella, Baesso Ilenia, Varotto Stefania, Albergoni Maria Paola, Boscaro Elisa, Cesaro Simone, Pillon Marta, Calore Elisabetta, Gazzola Maria Vittoria, Semenzato Gianpietro, Messina Chiara, Trentin Livio
Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute for Molecular Medicine (VIMM), Centro di Eccellenza per la Ricerca Biomedica, Padua, Italy.
Pediatr Transplant. 2011 Mar;15(2):198-204. doi: 10.1111/j.1399-3046.2010.01447.x.
In HSCT setting, KIR-driven alloreactivity might be better predicted if the donor KIR genotype is considered in addition to the recipient HLA genotype. The prediction of NK cell alloreactivity relies on the missing ligand in the recipient, a scenario that can be found in HLA-identical and non-identical allotransplants. The aim of this study was to investigate at genetic level the prognostic impact of recipient HLA-I lacking for donor KIR on allotransplanted patients outcome. We analysed donors KIR genotype and HLA genotype of 60 paediatric patients who received related (n=15) or unrelated (n=45) transplantation. When patients were grouped based on the KIR gene type involved in the KIR/HLA-I mismatch, we did not observe any relapse in the group of patients characterized by mismatches involving only inhibitory KIR. On the contrary, all relapses were observed in patients showing at least one activating gene involved in the mismatch (p<0.05). Although the biological mechanism accounting for this putative genetic rule is still to be clarified, we suggest that a careful survey of KIR/HLA-I mismatching should be taken into account in the selection of donor in related and unrelated HSCT.
在异基因造血干细胞移植（HSCT）背景下，如果除了考虑受者的HLA基因型外，还考虑供者的KIR基因型，可能会更好地预测KIR驱动的同种异体反应性。NK细胞同种异体反应性的预测依赖于受者中缺失的配体，这种情况在HLA相同和不同的同种异体移植中都可能出现。本研究的目的是在基因水平上研究供者KIR所对应的受者HLA-I缺失对同种异体移植患者预后的影响。我们分析了60例接受相关（n = 15）或无关（n = 45）移植的儿科患者的供者KIR基因型和HLA基因型。当根据参与KIR/HLA-I错配的KIR基因类型对患者进行分组时，我们在仅涉及抑制性KIR错配的患者组中未观察到任何复发情况。相反，在至少有一个参与错配的激活基因的患者中观察到了所有的复发情况（p<0.05）。尽管解释这一假定遗传规律的生物学机制仍有待阐明，但我们建议在相关和无关HSCT供者的选择中，应考虑对KIR/HLA-I错配进行仔细研究。
