Gene expression profiling at birth characterizing the preterm infant with early onset infection

Anne Hilgendorff,Benjamin Izar,Manuel Klein,Andre Billion,Joachim Kreuder,Ludwig Gortner,Christine Windemuth-Kieselbach,Michael Maier,Trinad Chakraborty,Anita Windhorst,Hamid Hossain,Svetlin Tchatalbachev,Matthias Heckmann,Harald Ehrhardt,Josef Mysliwietz,Anna Gkatzoflia

doi:10.1007/s00109-016-1466-4

Abstract

Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants.Key messageGene expression (GE) profiling at birth characterizes preterm infants with EOI.GE analysis indicates dysregulation of NK cell activity.NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.

Highlights

Preterm birth (PTB) remains a major problem in perinatal medicine and accounts for 75 % of the perinatal mortality and 50 % of the perinatal morbidity [1]
The analysis revealed a considerable overlap of functional categories and the corresponding genes when compared with the results derived from Rank Products only (Supplemental Tables 4 and 5), i.e., the findings obtained from adjusted gene expression data supported the results from the initial Rank Products analysis
We performed transcriptional profiling from umbilical arterial blood samples to obtain insights into the pathways involved in Impairment of natural killer (NK) cell function plays a critical role in the host response to infectious challenges in preterm infants with Early onset infections (EOI), but a comprehensive evaluation of their cell state is lacking [22]

Summary

Introduction

Preterm birth (PTB) remains a major problem in perinatal medicine and accounts for 75 % of the perinatal mortality and 50 % of the perinatal morbidity [1]. Onset infections (EOI) in PTB are associated with significant morbidity and a mortality rate of 15– 50 %, especially in very immature preterm infants [2, 3]. Clinical and experimental studies continue to provide valuable insight into processes leading to EOI and its attendant complications [4, 5], biological pathways relevant to the complex pathophysiology of EOI remain poorly understood. This is reflected in the limitations of early diagnostic markers and the absence of targeted treatment approaches in this high-risk patient cohort. As outcome and prognosis of EOI mainly depend on early and efficient treatment, sensitive and specific indicators of EOI are crucial at the earliest stage of disease

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Conclusion