DNA Methylation Analysis to Unravel Altered Genetic Pathways Underlying Early Onset and Late Onset Neonatal Sepsis. A Pilot Study

被引:16
作者
Lorente-Pozo, Sheila [1 ,2 ]
Navarrete, Paula [3 ]
Jose Garzon, Maria [3 ]
Lara-Canton, Inmaculada [1 ,2 ]
Beltran-Garcia, Jesus [4 ,5 ]
Osca-Verdegal, Rebeca [4 ,5 ]
Mena-Molla, Salvador [3 ,5 ]
Garcia-Lopez, Eva [3 ]
Vento, Maximo [1 ,2 ]
Pallardo, Federico, V [3 ,4 ,5 ]
Luis Garcia-Gimenez, Jose [3 ,4 ,5 ]
机构
[1] Hlth Res Inst La Fe, Neonatal Res Grp, Valencia, Spain
[2] Univ & Polytech Hosp La Fe, Div Neonatol, Valencia, Spain
[3] Parc Cientif Univ Valencia, EpiDis SL Spin Off CIBER ISCIII, Paterna, Spain
[4] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Valencia, Spain
[5] Univ Valencia INCLIVA, Fac Med & Odontol, Dept Fisiol, Valencia, Spain
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷
关键词
neonatology and pediatric intensive care; DNA methylation; sepsis; inflammation; immunosuppression; EARLY-DIAGNOSIS; EXPRESSION; CELLS; INTERLEUKIN-6; EPIGENETICS; DYSFUNCTION; MICROARRAY; PACKAGE; PATTERN;
D O I
10.3389/fimmu.2021.622599
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Neonatal sepsis is a systemic condition widely affecting preterm infants and characterized by pro-inflammatory and anti-inflammatory responses. However, its pathophysiology is not yet fully understood. Epigenetics regulates the immune system, and its alteration leads to the impaired immune response underlying sepsis. DNA methylation may contribute to sepsis-induced immunosuppression which, if persistent, will cause long-term adverse effects in neonates. Objective: To analyze the methylome of preterm infants in order to determine whether there are DNA methylation marks that may shed light on the pathophysiology of neonatal sepsis. Design: Prospective observational cohort study performed in the neonatal intensive care unit (NICU) of a tertiary care center. Patients: Eligible infants were premature <= 32 weeks admitted to the NICU with clinical suspicion of sepsis. The methylome analysis was performed in DNA from blood using Infinium Human Methylation EPIC microarrays to uncover methylation marks. Results: Methylation differential analysis revealed an alteration of methylation levels in genomic regions involved in inflammatory pathways which participate in both the innate and the adaptive immune response. Moreover, differences between early and late onset sepsis as compared to normal controls were assessed. Conclusions: DNA methylation marks can serve as a biomarker for neonatal sepsis and even contribute to differentiating between early and late onset sepsis.
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页数:13
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