Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-08-01
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| Series: | Pediatrics and Neonatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957218301281 |
| _version_ | 1818190073841057792 |
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| author | Tadamune Kinjo Hirosuke Inoue Takeshi Kusuda Junko Fujiyoshi Masayuki Ochiai Yasushi Takahata Satoshi Honjo Yuhki Koga Toshiro Hara Shouichi Ohga |
| author_facet | Tadamune Kinjo Hirosuke Inoue Takeshi Kusuda Junko Fujiyoshi Masayuki Ochiai Yasushi Takahata Satoshi Honjo Yuhki Koga Toshiro Hara Shouichi Ohga |
| author_sort | Tadamune Kinjo |
| collection | DOAJ |
| description | 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. Key Words: IL-8, liver fibrosis, MCP-1, myeloproliferative disorder, trisomy 21 |
| first_indexed | 2024-12-11T23:52:55Z |
| format | Article |
| id | doaj.art-f79526c67ab14b209cc364b7401e07e4 |
| institution | Directory Open Access Journal |
| issn | 1875-9572 |
| language | English |
| last_indexed | 2024-12-11T23:52:55Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj.art-f79526c67ab14b209cc364b7401e07e42022-12-22T00:45:26ZengElsevierPediatrics and Neonatology1875-95722019-08-01604382388Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesisTadamune Kinjo0Hirosuke Inoue1Takeshi Kusuda2Junko Fujiyoshi3Masayuki Ochiai4Yasushi Takahata5Satoshi Honjo6Yuhki Koga7Toshiro Hara8Shouichi Ohga9Department 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; Corresponding author. Fukuoka Children's Hospital, 5-1-1, Kashiiteriha, Higashi-ku, Fukuoka, 813-0017, Japan. Fax: +81 92 682 7300.Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Fukuoka Children's Hospital, Fukuoka, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, JapanFukuoka Children's Hospital, Fukuoka, JapanDepartment of Pediatrics, Fukuoka National Hospital, Fukuoka, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Fukuoka Children's Hospital, Fukuoka, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, JapanBackground: 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. Key Words: IL-8, liver fibrosis, MCP-1, myeloproliferative disorder, trisomy 21http://www.sciencedirect.com/science/article/pii/S1875957218301281 |
| spellingShingle | Tadamune Kinjo Hirosuke Inoue Takeshi Kusuda Junko Fujiyoshi Masayuki Ochiai Yasushi Takahata Satoshi Honjo Yuhki Koga Toshiro Hara Shouichi Ohga Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis Pediatrics and Neonatology |
| title | Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis |
| title_full | Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis |
| title_fullStr | Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis |
| title_full_unstemmed | Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis |
| title_short | Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis |
| title_sort | chemokine levels predict progressive liver disease in down syndrome patients with transient abnormal myelopoiesis |
| url | http://www.sciencedirect.com/science/article/pii/S1875957218301281 |
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