EVALUATION OF THE DIAGNOSTIC VALUE OF CYTOKINES AND MICRORNAS IN TERM NEWBORNS WITH CONGENITAL HEART DEFECTS AS BIOMARKERS OF NECROTIZING ENTEROCOLITIS
- Authors: Zaikova E.K.1, Kaplina A.V.1, Petrova N.A.1, Pervunina T.M.1, Kostareva A.A.1, Kalinina O.V.1,2
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Affiliations:
- Almazov National Medical Research Centre, St. Petersburg, Russia
- Saint-Petersburg Pasteur Institute, St. Petersburg, Russia
- Section: Immunological readings in Chelyabinsk
- Submitted: 29.03.2025
- Accepted: 25.05.2025
- URL: https://rusimmun.ru/jour/article/view/17136
- DOI: https://doi.org/10.46235/1028-7221-17136-EOT
- ID: 17136
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Abstract
Abstract
Newborns with ductus-dependent congenital heart defects (CHD) are at increased risk of developing necrotizing enterocolitis (NEC), a severe inflammatory bowel disease. Given that early symptoms of NEC are nonspecific, an urgent task is to find specific diagnostic biomarkers both for diagnosing NEC and for stratifying the risk of its development and implementing preventive measures. Promising NEC biomarkers are cytokines and microRNAs regulating various biological processes. The aim of the study was to evaluate the diagnostic potential of the levels of 31 cytokines and three microRNAs in the plasma of newborns with CHD as specific NEC biomarkers. The study included 38 term newborns with CHD who underwent cardiac surgery on the 8 [6;12] day of life, 10 of whom developed NEC postoperatively. Cytokine levels in plasma samples from 28 newborns without NEC and 10 newborns with NEC were measured using the MILLIPLEX Human Cytokine/Chemokine/Growth Factor Panel A kit (MilliporeSigma, USA) on a MAGPIX instrument (Luminex, USA). Total RNA was isolated from plasma samples of 14 newborns without NEC and 10 newborns with NEC using the TRIzol LS reagent (Thermo Fisher Scientific, USA) with the external synthetic control cel-miR-39-3p for subsequent data normalization. Expression levels of microRNA-155-5p, microRNA-221-3p, and microRNA-451a were measured using the TaqMan MicroRNA Reverse Transcription Kit (Thermo Fisher Scientific, USA) and TaqMan MicroRNA Assays (Life Technologies, USA). In newborns with NEC, the levels of IL-8 and M-CSF were 1.6 (p=0.037) and 12.6 (p=0.006) times higher, respectively, than in newborns without NEC. The relative expression of miR-451a was 5 times lower in newborns with NEC than in newborns without NEC. No significant differences in the levels of other analyzed cytokines and microRNAs were found. The model including three biomarkers miR-451a, IL-8 and M-CSF has a high diagnostic potential (AUC=0.901 with a sensitivity of 85.7% and a specificity of 84.6%) for the diagnosis of NEC in routine clinical practice.
About the authors
Ekaterina K. Zaikova
Almazov National Medical Research Centre, St. Petersburg, Russia
Email: catherine3452@yandex.ru
ORCID iD: 0000-0003-0584-2330
SPIN-code: 3605-5787
Scopus Author ID: 57214227133
ResearcherId: N-4913-2018
Junior Researcher of the Research Institute of Microvesicular Signaling, Institute of Molecular Biology and Genetics
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2Aleksandra V. Kaplina
Almazov National Medical Research Centre, St. Petersburg, Russia
Email: kaplinashi@gmail.com
ORCID iD: 0000-0001-6939-6961
SPIN-code: 4075-8304
Scopus Author ID: 57220003313
ResearcherId: AAQ- 8417-2021
Junior Researcher of the Research Laboratory of Physiology and Diseases of Newborns, Institute of Perinatology and Pediatrics, Neonatologist of Department of Neonatal Physiology with an ICU Ward, Perinatal Centre
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2Natalia A. Petrova
Almazov National Medical Research Centre, St. Petersburg, Russia
Email: natalja5@yandex.ru
ORCID iD: 0000-0002-0479-0850
SPIN-code: 9140-9743
Scopus Author ID: 55414973300
PhD, Associate Professor, Head of the Research Laboratory of Physiology and Diseases of Newborns, Institute of Perinatology and Pediatrics
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2Tatiana M. Pervunina
Almazov National Medical Research Centre, St. Petersburg, Russia
Email: ptm.pervunina@yandex.ru
ORCID iD: 0000-0001-9948-7303
SPIN-code: 3288-4986
Scopus Author ID: 56572907100
ResearcherId: ABI-7364-2020
MD, Professor, Director of the Institute of Perinatology and Pediatrics
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2Anna A. Kostareva
Almazov National Medical Research Centre, St. Petersburg, Russia
Email: akostareva@hotmail.com
ORCID iD: 0000-0002-9349-6257
SPIN-code: 5343-6287
Scopus Author ID: 8906596800
ResearcherId: H-2204-2016
MD, Professor of the Department of Faculty Therapy with the Clinic of the Institute of Medical Education, Director of the Institute of Molecular Biology and Genetics
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2Olga V. Kalinina
Almazov National Medical Research Centre, St. Petersburg, Russia;Saint-Petersburg Pasteur Institute, St. Petersburg, Russia
Author for correspondence.
Email: olgakalinina@mail.ru
ORCID iD: 0000-0003-1916-5705
SPIN-code: 7752-7929
Scopus Author ID: 56326552100
ResearcherId: L-1822- 2017
DSc., Professor of the Department of Laboratory Medicine with Clinic of the Institute of Medical Education, Leading Researcher of the Institute of Molecular Biology and Genetics, Leading Researcher of the Research Laboratory of Molecular Epidemiology and Genetics Evolution
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2References
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