Wahlund Martina, Lindqvist Appell Malin, Hed Myrberg Ida, Berggren Anna, Nilsson Anna
Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, 171 64 Stockholm, Sweden.
Department of Clinical Microbiology, Karolinska University Hospital, 171 64 Stockholm, Sweden.
Children (Basel). 2020 Dec 16;7(12):296. doi: 10.3390/children7120296.
Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for , , and were investigated in relation to clinical utility of identifying severe episodes of febrile neutropenia (FN) in a cohort of children undergoing treatment for acute lymphoblastic leukemia. The study included 122 children, where data on FN and microbiological findings were retrospectively collected from medical records. Sequence variants in genes coding for , , and were identified by pyrosequencing, TaqMan SNP genotyping assay, and gel electrophoresis. A total of 380 episodes of FN were identified and in 139 episodes, there was a microbiological defined infection. Age and treatment intensity were all associated with the risk of developing FN. No sequence variant was associated to increased numbers of FN episodes. Two sequence variants in the gene increased the risk of viral infection, whilst sequence variants in the gene were associated to a decreased risk of bacterial blood-stream infection (BSI). The investigated sequence variants did not associate with increased risk for FN or to severe infections, as to why the clinical utility as a risk-stratification tool is low. Most episodes of FN were classified as fever with unknown origin, emphasizing the need for improved microbial detection methods.
先前已发现,参与免疫系统的基因中的序列变异与中性粒细胞减少症以及癌症患者的感染有关。在一组接受急性淋巴细胞白血病治疗的儿童中,对编码 、 和 的基因中的序列变异与识别严重发热性中性粒细胞减少症(FN)发作的临床效用进行了研究。该研究纳入了122名儿童,从病历中回顾性收集了有关FN和微生物学检查结果的数据。通过焦磷酸测序、TaqMan SNP基因分型检测和凝胶电泳鉴定编码 、 和 的基因中的序列变异。共识别出380次FN发作,其中139次发作存在微生物学定义的感染。年龄和治疗强度均与发生FN的风险相关。没有序列变异与FN发作次数增加相关。 基因中的两个序列变异增加了病毒感染的风险,而 基因中的序列变异与细菌性血流感染(BSI)风险降低相关。所研究的序列变异与FN风险增加或严重感染无关,因此作为风险分层工具的临床效用较低。大多数FN发作被归类为不明原因发热,这凸显了改进微生物检测方法的必要性。