Abteilung Hämatologie/Internistische Onkologie, Klinik für Innere Medizin II, Jena University Hospital, Erlanger Allee 101, Jena, Germany.
Ann Hematol. 2013 Aug;92(8):1071-7. doi: 10.1007/s00277-013-1734-0. Epub 2013 Apr 5.
We sought to investigate the relationship between polymorphisms of the NOD2 gene and infectious complications following intensive induction chemotherapy in patients with acute myeloid leukaemia (AML). We hypothesised that single nucleotide polymorphisms (SNPs) of the NOD2 gene are associated with a higher rate of infections during the phase of severe neutropenia. In 131 AML patients receiving induction therapy, the presence of the three most frequent polymorphisms of NOD2 (Arg702Trp, Gly908Arg, Leu1007fsinsC) was analysed. SNP analyses by means of genomic PCR incorporating fluorescence-labelled probes with characteristic melting curves were performed using the LightCycler platform. Our data suggest a significantly lower probability of mucositis or enteritis in AML patients lacking any of the three evaluated NOD2 polymorphisms. Furthermore, bloodstream cultures of AML patients carrying either a missense or a frameshift mutation of NOD2 were significantly more frequently tested positive concerning Streptococcus spp. In contrast, the presence of NOD2 polymorphisms had no impact on such important infectious complications as systemic inflammatory response syndrome or sepsis, the rate of central venous catheter infections or the incidence of pneumonia including fungal infections. Our data represent one of the first reports investigating the impact of polymorphisms of the innate immune system on infectious complications in patients with neutropenia following chemotherapy. A correlation between NOD2 polymorphisms and infectious events in AML patients is demonstrated.
我们旨在探讨 NOD2 基因多态性与急性髓系白血病(AML)患者强化诱导化疗后感染并发症之间的关系。我们假设 NOD2 基因的单核苷酸多态性(SNP)与严重中性粒细胞减少期感染率较高有关。在接受诱导治疗的 131 例 AML 患者中,分析了 NOD2 (Arg702Trp、Gly908Arg、Leu1007fsinsC)三种最常见的多态性的存在情况。通过结合具有特征性熔解曲线的荧光标记探针的基因组 PCR 进行 SNP 分析,使用 LightCycler 平台进行。我们的数据表明,在缺乏三种评估的 NOD2 多态性之一的 AML 患者中,粘膜炎或肠炎的发生概率显著降低。此外,携带 NOD2 错义或移码突变的 AML 患者的血流培养物中,链球菌属的检测阳性率显著更高。相比之下,NOD2 多态性的存在对全身性炎症反应综合征或败血症等重要感染并发症、中心静脉导管感染率或包括真菌感染在内的肺炎发生率没有影响。我们的数据代表了首批研究化疗后中性粒细胞减少症患者固有免疫系统多态性对感染并发症影响的报告之一。证明了 NOD2 多态性与 AML 患者感染事件之间的相关性。