Cytokine Levels at Birth in Children Who Developed Acute Lymphoblastic Leukemia.
Cytokine Levels at Birth in Children Who Developed Acute Lymphoblastic Leukemia.
复制标题
DOI：
10.1158/1055-9965.epi-20-1704
复制
发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Metayer C
中科院分区：
文献类型：
--
作者：
Whitehead TP;Wiemels JL;Zhou M;Kang AY;McCoy LS;Wang R;Fitch B;Petrick LM;Yano Y;Imani P;Rappaport SM;Dahl GV;Kogan SC;Ma X;Metayer C
产前免疫发育可能在儿童急性淋巴细胞白血病（ALL）的病因学中起重要作用。7种细胞因子-白细胞介素1β (il - 1β), il - 4, il - 6, il - 8，粒细胞-巨噬细胞集落刺激因子（GM-CSF），肿瘤坏死因子α (tnf - α)和血管内皮生长因子(VEGF) -分析了1020例ALL患者和1003名参加加州儿童白血病研究的对照组出生时收集的血斑。使用社会人口统计学和出生特征调整的逻辑回归计算与细胞因子水平四分位数范围增量相关的比值比（ORs）和95%置信区间（95% CI）。我们发现ALL患者出生时一组相关细胞因子的水平高于对照组[il - 1β: OR为1.18 (95% CI: 1.03, 1.35)；Il8: 1.19 (1.03, 1.38)；Tnfα: 1.15 (1.01, 1.30)；VEGF: 1.16(1.01, 1.33)]，尤其是拉丁裔母亲的孩子（or从1.31到1.40）和ALL高二倍体（or高达1.27）。我们发现新生儿细胞因子水平与新生儿内源性代谢物水平相关，而内源性代谢物水平先前与ALL风险相关；然而，没有证据表明细胞因子介导了这些代谢物与ALL风险之间的关系。我们假设，出生时细胞因子水平改变的儿童，其后续异常免疫反应的风险增加，从而引发ALL。这是第一个评估出生时免疫调节细胞因子水平、产前暴露和儿童ALL风险之间相互作用的研究。
Prenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL). Seven cytokines – interleukin 1β (IL1β), IL4, IL6, IL8, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα), and vascular endothelial growth factor (VEGF) – were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. Odds ratios (ORs) and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression adjusting for sociodemographic and birth characteristics. We found that ALL patients were born with higher levels of a group of correlated cytokines than controls [IL1β: OR of 1.18 (95% CI: 1.03, 1.35); IL8: 1.19 (1.03, 1.38); TNFα: 1.15 (1.01, 1.30); VEGF: 1.16 (1.01, 1.33)], especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk. We posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL. This is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.