Centre Hospitalier de Québec-Université Laval Research Center, Québec, G1V 4G2, Canada.
Department of Pediatrics, Université Laval, Québec, G1V 0A6, Canada.
Immun Inflamm Dis. 2018 Dec;6(4):428-434. doi: 10.1002/iid3.232. Epub 2018 Jul 20.
Dickkopf-1 (DKK1) is a soluble protein and antagonist of the Wnt/β-catenin signaling pathway. DKK1 is found elevated in serum from patients affected with various types of cancers and in some instances, it is considered a diagnostic and prognostic biomarker. Elevated serum levels of DKK1 have also been detected in animal models of chronic inflammatory diseases. Previous work from our laboratory has demonstrated upregulation of DKK1 in cells and mouse models of the bone marrow failure (BMF) and cancer-prone disease Fanconi anemia (FA). The present study aimed to investigate whether DKK1 blood levels in patients are associated with FA or inflammatory responses to acute infections.
Plasma samples were collected from 58 children admitted to the Centre Mère-Enfant Soleil du Centre Hospitalier de Québec-Université Laval with signs of acute infections. Blood plasma specimens were also collected from healthy blood donors at the Héma-Québec blood donor clinic. Plasmas from patients diagnosed with FA were also included in the study. DKK1 levels in blood plasmas were assessed by standard ELISA.
Patients with acute infections showed dramatically high levels of DKK1 (6072 ± 518 pg/ml) in their blood compared to healthy blood donors (1726 ± 95 pg/ml). No correlations were found between DKK1 levels and C reactive protein (CRP) concentration, platelet numbers, or white blood cell counts. Patients with FA showed higher DKK1 plasma levels (3419 ± 147.5 pg/ml) than healthy blood donors (1726 ± 95 pg/ml) but significantly lower than patients with acute infections.
These findings suggest that blood DKK1 is elevated in response to infections and perhaps to inflammatory responses.
Dickkopf-1（DKK1）是一种可溶性蛋白，也是 Wnt/β-连环蛋白信号通路的拮抗剂。DKK1 在受各种类型癌症影响的患者的血清中升高，在某些情况下，它被认为是一种诊断和预后的生物标志物。在慢性炎症性疾病的动物模型中也检测到血清 DKK1 水平升高。我们实验室的先前工作表明，DKK1 在骨髓衰竭（BMF）和癌症易患疾病范可尼贫血（FA）的细胞和小鼠模型中上调。本研究旨在探讨患者的 DKK1 血液水平是否与 FA 或对急性感染的炎症反应有关。
从因急性感染到魁北克大学拉瓦尔中心医院母子太阳中心就诊的 58 名儿童中采集血浆样本。还从 Héma-Quebec 献血者诊所的健康献血者中采集血液血浆标本。患有 FA 的患者的血浆也包括在研究中。通过标准 ELISA 评估血液血浆中的 DKK1 水平。
与健康献血者（1726±95pg/ml）相比，患有急性感染的患者血液中 DKK1 水平（6072±518pg/ml）显着升高。未发现 DKK1 水平与 C 反应蛋白（CRP）浓度、血小板计数或白细胞计数之间存在相关性。FA 患者的 DKK1 血浆水平（3419±147.5pg/ml）高于健康献血者（1726±95pg/ml），但明显低于急性感染患者。
这些发现表明，血液 DKK1 升高是对感染的反应，也许是对炎症反应的反应。
