Circulating miRNA as an early indicator of infectious inflammatory diseases in the newborns

• Timofeeva A.V.
• Irina V. Nikitina
• Gusar V.A.
• Vitaliy V. Chagovets
• Anna R. Kirtbaya
• Oleg V. Ionov
• Dmitriy N. Degtyarev
• Natalia E. Kan
• Vladimir E. Frankevich

Abstract

Infectious inflammatory diseases in newborns remain the main cause of the death in neonatal period. They occurred in the setting of the morphofunctional dismaturity of immune system and often paucisymptomatic. The assessment of the specific biomarkers for non-invasive diagnostics and treatment of these diseases is currently important. One of the key regulators of the body system is small non-coding RNAs. miRNAs used for non-invasive diagnostics of a wide range of diseases.

Aim: analysis of the expression level of miRNAs that potentially regulates translation of IL-1β, IL-6, IL-8, IL10, IL13, TNF-α, IFNγ, CCL2 in the peripheral blood plasma of newborns. Newborns of the first day of life with the different gestational ages with respiratory disorders by infectious and non-infectious nature were evaluated.

Material and methods. Real-time RT-PCR was used to quantify hsa-miR-16-5p, -92a-3p, -130a-3p, -223-3p in 81 blood plasma samples of 3 groups of newborns divided by gestational age: 25-28, 29-31 and 32-40 weeks. Serum Plasma kit, miScript® II RT kit, SYBR Green PCR Kit (Qiagen, Germany) were used in the study.

Results. RT-PCR evaluated a significant increase in the expression level of hsa-miR-92a-3p and hsa-miR-130a-3p in the case of diagnosed congenital pneumonia (CP) and early neonatal sepsis (ENS). Statistical analysis revealed a significant correlation between the level of an expression of hsa-miR-16-5p, -92a-3p, -130a-3p, -223-3p and CP; hsa-miR-16-5p, -92a-3p and ENS; hsa-miR-92a-3p and NEOMOD score's scale. The possibility of differential diagnosis of CP and ENS by the expression level of hsa-miR-16-5p and hsa-miR-130a-3p in blood plasma was demonstrated for the group of newborns of 25-31 GA. Statistic significant Spearman correlation were found for CP or ENS. These findings related between the level of hsa-miR-16-5p expression in intraventricular hemorrhage (IVH) and Silverman Score for study groups.

Conclusions. For the first time, the significant changes in the expression level of hsa-miR-16-5p, -92a-3p, -130a-3p, -223-3p in the blood plasma of newborns of various gestational age were demonstrated. We suspected that these findings will use as important tool for the differential diagnosis of CP, ENS and IVH. The miRNA expression level detection in the blood plasma of newborns can allow for more accurate and early diagnosis of infectious inflammatory diseases: CP and ENS, especially among extremely preterm newborns.

Keywords:miRNA, peripheral blood plasma, real-time RT-PCR, congenital pneumonia, early neonatal sepsis, intraventricular hemorrhage, newborn

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