Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.
Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.
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DOI：
10.1016/j.pedneo.2018.09.005
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发表时间：
2019-08
影响因子：
2.1
通讯作者：
T. Kinjo;Hirosuke Inoue;Takeshi Kusuda;Junko K. Fujiyoshi;M. Ochiai;Y. Takahata;S. Honjo;Yuhki Koga;T. Hara;S. Ohga
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作者：
T. Kinjo;Hirosuke Inoue;Takeshi Kusuda;Junko K. Fujiyoshi;M. Ochiai;Y. Takahata;S. Honjo;Yuhki Koga;T. Hara;S. Ohga
研究背景短暂性骨髓生成异常（TAM）是一种新生儿白血病前期综合征，仅发生于唐氏综合征（DS）新生儿。大多数受影响的婴儿自发解决，虽然一些患者最终在肝功能衰竭，尽管血液学缓解。不可能确定哪些患者具有进行性肝病和白血病转化的高风险。目的是寻找生物标志物，预测肝衰竭的发展，在DS婴儿与TAM。MethodsAmong 60新生儿DS连续入院到我们的机构从2003年至2016年，41名婴儿与或没有TAM入组的研究。22例TAM患者被分为需要任何治疗的“进展组”（n = 7）和“自发消退组”（n = 15）。血清中趋化因子（CXCL 8，CXCL 9，CXCL 10，CCL 2和CCL 5）和转化生长因子（TGF）-β1的浓度测定在诊断TAM进行性diseases.ResultsThree患者发展白血病在研究期间（中位数，1147天;范围，33-3753）的结果进行评估。3例死于肝功能衰竭。进展组早产均<37孕周，早于自然消退组（中位数34.7 vs.37.0周，P < 0.01）。进展组诊断时的白细胞计数和CXCL 8和CCL 2水平高于自发消退组（白细胞：中位数，81.60vs.27.30 × 109/L，p = 0.01; CXCL 8：173.8 vs.34.3 pg/mL，p < 0.01; CCL 2：790.3 vs.209.8 pg/mL，p < 0.01）。多变量分析表明，CCL 2值升高与肝衰竭进展独立相关，CXCL 8值升高与肝衰竭死亡独立相关（CCL 2：标准化系数[sc]，0.43，p < 0.01; CXCL 8：sc =-0.46，p = 0.02）。
BackgroundTransient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM.MethodsAmong 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into “progression group” (n = 7) that required any therapy and “spontaneous resolution group” (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease.ResultsThree patients developed leukemia during the study period (median, 1147 days; range, 33–3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7vs.37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60vs.27.30 × 109/L, p = 0.01; CXCL8: 173.8vs.34.3 pg/ml, p < 0.01; CCL2: 790.3vs.209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = −0.46, p = 0.02).ConclusionHigh levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.