Pediatric Hemato-Oncology Research Laboratory, Sackler Faculty of Medicine, Department of Pediatric Hemato-Oncology, Tel Aviv Medical Center, Tel Aviv, Israel.
Pediatric Hemato-Oncology Research Laboratory, Sackler Faculty of Medicine, Department of Pediatric Hemato-Oncology, Tel Aviv Medical Center, Tel Aviv, Israel; Department of Pediatric Hemato-Oncology, Sackler Faculty of Medicine, Tel Aviv Medical Center, Tel Aviv, Israel.
Biol Blood Marrow Transplant. 2019 Dec;25(12):2350-2356. doi: 10.1016/j.bbmt.2019.07.032. Epub 2019 Aug 5.
Impaired neutrophil extracellular trap (NET) formation compromises the host defense after engraftment following hematopoietic stem cell transplantation (HSCT) despite adequate neutrophil counts. The aims of the present study were to determine reference ranges for the activity of key enzymes of NET formation-neutrophil elastase (NE) and myeloperoxidase (MPO)-in a healthy population and to unravel the recovery dynamics of NET formation over time following HSCT, along with NE and MPO enzymatic activities. Reference ranges of NE and MPO activity were derived from 50 healthy volunteers. During 2017 to 2018, 11 consecutive pediatric patients undergoing allogeneic or autologous HSCT were recruited at a single referral center for pediatric hemato-oncology. Patients were followed for up to 1 year following engraftment. The mean reference value was 7.5 ± .4 mU for NE activity and 2.17 ± .4 U for MPO activity in the healthy population, and enzymatic activity of MPO was significantly higher in males. At 3 weeks following neutrophil engraftment, all study participants demonstrated extremely low enzymatic NE activity, whereas MPO activity was above the lower normal reference range at all time points. Reduced NE activity corresponded to the inability to form NETs. Neutrophil function improved over time, but partial impairment persisted for 7 months following transplantation. The ability of neutrophils to form NETs was significantly impaired for 3 weeks after engraftment in the setting of HSCT, exposing patients to bacterial infections. NE activity might serve as a surrogate marker for the capacity of neutrophils to form NETs.
中性粒细胞胞外诱捕网（NET）形成受损会削弱造血干细胞移植（HSCT）后中性粒细胞计数充足时的宿主防御能力。本研究的目的是确定健康人群中 NET 形成关键酶-中性粒细胞弹性蛋白酶（NE）和髓过氧化物酶（MPO）的活性参考范围，并揭示 HSCT 后 NET 形成随时间的恢复动态以及 NE 和 MPO 酶活性。NE 和 MPO 活性的参考范围来自 50 名健康志愿者。在 2017 年至 2018 年期间，在一家儿科血液肿瘤学的单转诊中心招募了 11 名连续接受同种异体或自体 HSCT 的儿科患者。患者在移植后随访长达 1 年。健康人群中 NE 活性的平均参考值为 7.5 ±.4 mU，MPO 活性为 2.17 ±.4 U，男性 MPO 酶活性明显较高。在中性粒细胞植入后 3 周，所有研究参与者的 NE 酶活性均极低，而 MPO 活性在所有时间点均高于正常下限。NE 活性降低对应于无法形成 NET。随着时间的推移，中性粒细胞功能有所改善，但移植后 7 个月仍存在部分损伤。在 HSCT 背景下，中性粒细胞形成 NET 的能力在植入后 3 周内显著受损，使患者容易发生细菌感染。NE 活性可以作为中性粒细胞形成 NET 能力的替代标志物。
