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

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 × 109/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.

• Authors: Tadamune Kinjo, Hirosuke Inoue, Takeshi Kusuda, Junko Fujiyoshi, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Yuhki Koga, Toshiro Hara, Shouichi Ohga
• Journal: Pediatrics and neonatology (Pediatr Neonatol) Vol. 60 Issue 4 Pg. 382-388 (08 2019) ISSN: 2212-1692 [Electronic] Singapore
• PMID: 30314728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• CCL2 protein, human
• CCL5 protein, human
• CXCL10 protein, human
• CXCL8 protein, human
• CXCL9 protein, human
• Chemokine CCL2
• Chemokine CCL5
• Chemokine CXCL10
• Chemokine CXCL9
• Chemokines
• Interleukin-8
• TGFB1 protein, human
• Transforming Growth Factor beta1

Topics

• Case-Control Studies
• Chemokine CCL2 (blood)
• Chemokine CCL5 (blood)
• Chemokine CXCL10 (blood)
• Chemokine CXCL9 (blood)
• Chemokines (blood)
• Cohort Studies
• Disease Progression
• Down Syndrome (blood, complications)
• Female
• Humans
• Hyperbilirubinemia (epidemiology)
• Infant
• Infant, Newborn
• Infant, Premature
• Interleukin-8 (blood)
• International Normalized Ratio
• Leukemia
• Leukemia, Megakaryoblastic, Acute (blood, epidemiology)
• Leukemoid Reaction (blood, complications)
• Liver Failure (blood, epidemiology, etiology)
• Male
• Mortality
• Premature Birth (epidemiology)
• Prognosis
• Prothrombin Time
• Risk Assessment
• Transforming Growth Factor beta1 (blood)