趋化因子水平可预测伴有短暂性髓系增生异常的唐氏综合征患者进行性肝脏疾病。

Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.

机构信息

Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan; Fukuoka Children's Hospital, Fukuoka, Japan.

Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.

出版信息

Pediatr Neonatol. 2019 Aug;60(4):382-388. doi: 10.1016/j.pedneo.2018.09.005. Epub 2018 Sep 24.

DOI:10.1016/j.pedneo.2018.09.005

PMID:30314728

Abstract

BACKGROUND

Transient 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.

METHODS

Among 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.

RESULTS

Three 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, 34.7 vs. 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, 81.60 vs. 27.30 × 10/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 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).

CONCLUSION

High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.

摘要

背景

短暂性髓系细胞增生异常（TAM）是一种新生儿前白血病综合征，仅发生在唐氏综合征（DS）新生儿中。大多数受影响的婴儿会自行缓解，尽管一些患者尽管血液学缓解，但最终会发展为肝功能衰竭。无法确定哪些患者有进展性肝病和白血病转化的高风险。目的是寻找预测 TAM 合并 DS 婴儿肝功能衰竭发展的生物标志物。

方法

2003 年至 2016 年期间，我们机构连续收治 60 名唐氏综合征新生儿，其中 41 名患有或不患有 TAM 的婴儿被纳入研究。22 名 TAM 患儿分为“进展组”（n=7），需要任何治疗和“自发缓解组”（n=15）。在 TAM 诊断时测量趋化因子（CXCL8、CXCL9、CXCL10、CCL2 和 CCL5）和转化生长因子（TGF）-β1 的血清浓度，以评估疾病进展的结果。

结果

在研究期间，3 名患者发生白血病（中位时间，1147 天；范围，33-3753）。3 名患者死于肝功能衰竭。进展组的所有患者均为早产<37 周的妊娠期，且早于自发缓解组（中位数，34.7 周与 37.0 周，p<0.01）。进展组在诊断时的白细胞计数和 CXCL8 和 CCL2 水平高于自发缓解组（白细胞：中位数，81.60 与 27.30×10/L，p=0.01；CXCL8：173.8 与 34.3 pg/ml，p<0.01；CCL2：790.3 与 209.8 pg/mL，p<0.01）。多变量分析表明，CCL2 值升高与进展相关，CXCL8 值与肝功能衰竭死亡相关（CCL2：标准化系数 [sc]，0.43，p<0.01；CXCL8：sc=-0.46，p=0.02）。