Espinoza J Luis, Wadasaki Yohei, Takami Akiyoshi
Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka, Japan.
Division of Hematology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Japan.
Front Microbiol. 2018 Oct 2;9:2317. doi: 10.3389/fmicb.2018.02317. eCollection 2018.
Hematopoietic stem cell transplantation (HSCT) is a highly advanced technique that offers a potential cure for an increasing number of life-threatening diseases. Enormous progress achieved in the last decade, including the refinement of donor selection and advancements in patient supportive care, had significantly improved transplant outcomes; however, invasive infections, graft-vs.-host disease (GVHD) and other serious complications still represent a major source of morbidity and mortality in HSCT recipients. The damage of anatomical barriers due to pre-transplant conditioning, a severely damaged immune function and a profound disruption in the composition of gut microbial commensals (gut microbiota) are alterations inherent to the transplant procedure that are directly implicated in the development of invasive infections and other HSCT complications. Although HLA-matching represents the most important genetic predictor of transplant outcomes, genetic variants in non-HLA genes, especially single nucleotide polymorphisms (SNPs) of genes encoding proteins associated with the immune response to tissue injury and pathogen infection have also been proposed as additional risk factors implicated in the occurrence of HSCT complications. Furthermore, although the microbiota composition is affected by several factors, recent evidence suggests that certain host genetic variants are associated with an altered composition of the gut microbiome and may, therefore, predispose some individuals to invasive infectious complications. This article summarizes the current understanding of the influence that genetic variants in non-HLA genes have on the development of infectious complications in HSCT recipients.
造血干细胞移植（HSCT）是一项高度先进的技术，为越来越多危及生命的疾病提供了潜在的治愈方法。过去十年取得了巨大进展，包括供体选择的优化和患者支持治疗的进步，显著改善了移植结果；然而，侵袭性感染、移植物抗宿主病（GVHD）和其他严重并发症仍然是HSCT受者发病和死亡的主要原因。移植前预处理导致的解剖屏障破坏、严重受损的免疫功能以及肠道微生物共生体（肠道微生物群）组成的深刻紊乱是移植过程中固有的改变，直接与侵袭性感染和其他HSCT并发症的发生有关。尽管HLA匹配是移植结果最重要的遗传预测指标，但非HLA基因的遗传变异，尤其是编码与组织损伤和病原体感染免疫反应相关蛋白质的基因的单核苷酸多态性（SNP），也被认为是HSCT并发症发生的额外危险因素。此外，尽管微生物群组成受多种因素影响，但最近的证据表明，某些宿主遗传变异与肠道微生物组组成的改变有关，因此可能使一些个体易患侵袭性感染并发症。本文总结了目前对非HLA基因遗传变异对HSCT受者感染并发症发生影响的认识。
