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埃及患者异基因造血干细胞移植后HLA - E多态性与临床结局

HLA-E polymorphism and clinical outcome after allogeneic hematopoietic stem cell transplantation in Egyptian patients.

作者信息

Mossallam Ghada I, Fattah Raafat Abdel, El-Haddad Alaa, Mahmoud Hossam K

机构信息

Bone Marrow Transplantation Laboratory Unit, National Cancer Institute, Cairo University, Cairo, Egypt.

Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Hum Immunol. 2015 Mar;76(2-3):161-5. doi: 10.1016/j.humimm.2014.12.017. Epub 2014 Dec 25.

DOI:10.1016/j.humimm.2014.12.017
PMID:25543014
Abstract

UNLABELLED

Human leukocyte antigen-E (HLA)-E in a non-classical major histocompatibility complex (MHC) class I (Ib) molecule. HLA-E-peptide complex acts as a ligand for natural killer (NK) cells and CD8+ T lymphocytes playing a dual role in natural and acquired immune responses. The difference in expression levels between HLA-E alleles was suggested to have impact on transplantation outcome. The aim of the study is to evaluate the clinical effect of HLA-E alleles on transplantation in a group of Egyptian patients. HLA-E genotyping was analyzed in eighty-eight recipients of stem cell transplantation using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). HLA-E01:03 allele showed a trend towards lower cumulative incidence of relapse at 2 years compared to homozygous HLA-E01:01 genotype (8% versus 21.5%, p=0.09, HR: 0.30, 95% CI: 0.91-1.69). HLA-E was the only factor showing near significant association with relapse incidence. HLA-E polymorphism did not affect the cumulative incidence of acute GVHD grades II-IV at 100 days, the 2-year cumulative incidence of extensive chronic GVHD, transplant related mortality (TRM) or overall survival (OS).

CONCLUSION

the suggested association of HLA-E polymorphism with reduced risk of relapse needs verification in a larger cohort. However, its proposed role in GVL helps better understanding of alloreactivity of T cells and NK cells and their implication in immunotherapy post allogeneic hematopoietic stem cell transplantation.

摘要

未标记

人类白细胞抗原-E(HLA)-E是一种非经典的主要组织相容性复合体(MHC)I类(Ib)分子。HLA-E-肽复合物作为自然杀伤(NK)细胞和CD8+T淋巴细胞的配体,在天然免疫和获得性免疫反应中发挥双重作用。HLA-E等位基因表达水平的差异被认为对移植结果有影响。本研究的目的是评估一组埃及患者中HLA-E等位基因对移植的临床效果。使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对88例干细胞移植受者进行HLA-E基因分型分析。与纯合子HLA-E01:01基因型相比,HLA-E01:03等位基因在2年时显示出复发累积发生率较低的趋势(8%对21.5%,p=0.09,HR:0.30,95%CI:0.91-1.69)。HLA-E是唯一与复发发生率显示出近乎显著关联的因素。HLA-E多态性不影响100天时急性移植物抗宿主病(GVHD)II-IV级的累积发生率、广泛慢性GVHD的2年累积发生率、移植相关死亡率(TRM)或总生存期(OS)。

结论

HLA-E多态性与复发风险降低之间的推测关联需要在更大的队列中进行验证。然而,其在移植物抗白血病(GVL)中的拟议作用有助于更好地理解T细胞和NK细胞的同种异体反应性及其在异基因造血干细胞移植后免疫治疗中的意义。

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