Low-Copy Number Polymorphism in DEFA1/DEFA3 Is Associated with Susceptibility to Hospital-Acquired Infections in Critically Ill Patients.

Jialian Zhao,Qiang Shu,Qiang Gu,Lifeng Wang,Weize Xu,Ya Wang,Zhongwang Li,Jianguo Xu,Lihua Chu,Xiangming Fang,Shuijing Wu,Zhiyong Hu

doi:10.1155/2018/2152650

Abstract

DEFA1/DEFA3, genes encoding human neutrophil peptides (HNP) 1–3, display wide-ranging copy number variations (CNVs) and is functionally associated with innate immunity and infections. To identify potential associations between DEFA1/DEFA3 CNV and hospital-acquired infections (HAIs), we enrolled 106 patients with HAIs and 109 controls in the intensive care unit (ICU) and examined their DEFA1/DEFA3 CNVs. DEFA1/DEFA3 copy number ranged from 2 to 16 per diploid genome in all 215 critically ill patients, with a median of 7 copies. In HAIs, DEFA1/DEFA3 CNV varied from 2 to 12 with a median of 6, which was significantly lower than that in controls (2 to 16 with a median of 8, p = 0.017). Patients with lower DEFA1/DEFA3 copy number (CNV < 7) were far more common in HAIs than in controls (52.8% in HAIs versus 35.8% in controls; p = 0.014; OR, 2.010; 95% CI, 1.164–3.472). The area under the receiver operating characteristic (AUROC) of DEFA1/DEFA3 CNV combined with clinical characteristics to predict the incidence of HAIs was 0.763 (95% CI 0.700–0.827), showing strong predictive ability. Therefore, lower DEFA1/DEFA3 copy number contributes to higher susceptibility to HAIs in critically ill patients, and DEFA1/DEFA3 CNV is a significant hereditary factor for predicting HAIs.

Highlights

Hospital-acquired infections (HAIs) are considered one of the most frequent adverse events that threaten patients’ safety in healthcare settings throughout the world [1,2,3]
Infection was defined as hospital acquired when it originated in the hospital environment and appeared 48 hours or more following admission [21], which was diagnosed based on the US Centers for Disease Control and Prevention (CDC) and National Healthcare Safety Network (NHSN) criteria [22]
In the HAIs group, eleven HAIs patients were excluded from the study due to intensive care unit (ICU) stays less than 48 hours (n = 6), young age (n = 1), or receipt of immunosuppressive therapy (n = 4)

Summary

Introduction

Hospital-acquired infections (HAIs) are considered one of the most frequent adverse events that threaten patients’ safety in healthcare settings throughout the world [1,2,3]. HAIs have become a serious issue in ICUs due to their high morbidity (nearly 15.1–47.9% all over the world), high mortality (27.6% or even higher), prolonged length of hospital stay, and increased economic burden [6], but there are no efficient tools for predicting HAIs. Studies show that among critically ill patients, the immune system undergoes simultaneous activation and suppression, leading to severe and persistent immune dysregulation [7, 8], and immune suppression may contribute to increased risk for HAIs. Defensins are small cationic, amphiphilic, cysteine-rich peptides produced by certain leukocytes and epithelial cells and comprise the front line of innate immune defense against pathogens [9,10,11].

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Results

Conclusion