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Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia.

ABSTRACT: Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-related gene expression patterns following standard methods to identify markers for oxygen utilization and BPD as outcomes in extremely premature infants. We further identified predictor gene sets for BPD based on transcriptomic data adjusted for gestational age at birth (GAB). RNA-Seq analysis was completed for CD8+ T cells from 145 subjects. Among the subjects with highest risk for BPD (born at <29 weeks gestational age (GA); n=72), 501 genes were associated with oxygen utilization. In the same set of subjects, 571 genes were differentially expressed in subjects with a diagnosis of BPD and 105 genes were different in BPD subjects as defined by physiologic challenge. A set of 92 genes could predict BPD with a moderately high degree of accuracy. We consistently observed dysregulation of TGFB, NRF2, HIPPO, and CD40-associated pathways in BPD. Using gene expression data from both premature and full-term subjects (n=116), we identified a 28 gene set that predicted the PRD status with a moderately high level of accuracy, which also were involved in TGFB signaling. Transcriptomic data from sort-purified peripheral blood CD8+ T cells from 145 preterm and full-term infants identified sets of molecular markers of inflammation associated with independent development of BPD in extremely premature infants at high risk for the disease and of PRD among the preterm and full-term subjects.

SUBMITTER: Bhattacharya S

PROVIDER: S-EPMC7859626 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia.

Bhattacharya Soumyaroop S Mereness Jared A JA Baran Andrea M AM Misra Ravi S RS Peterson Derick R DR Ryan Rita M RM Reynolds Anne Marie AM Pryhuber Gloria S GS Mariani Thomas J TJ

Frontiers in immunology 20210121

Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Premat ...[more]

PMID: 33552042

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Project description:ObjectivesWe investigated the genomic and metabolic characteristics of the airway microbiome in mild, moderate, severe, and non-bronchopulmonary dysplasia (BPD) preterm infants and explored possible mechanisms underlying BPD.MethodsTwenty-eight preterm infants with gestational age ≤34 weeks and intubated within 24 h after birth were enrolled. According to the severity of BPD, the patients were divided into mild, moderate and severe BPD groups, and the non-BPD group was the control group. Tracheal aspirates (TA) were obtained at intubation and on day 7 after birth. The bacterium in the aspirates were sequenced by 16S rRNA, and the metabolomics of the aspirates were identified by high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS). The correlation between the differential metabolite and differential bacteria was investigated using Pearson's correlation coefficient corrected for gestational age and birth weight and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases.ResultsThere were significant differences in the diversity and composition of airway microbiome and metabolome between severe, moderate and mild BPD and non-BPD premature infants. At birth (day 1), the difference was more pronounced than at day 7. The diversity of airway microbial community decreased, the abundance of Stenotrophomonas increased, and the increased level of sn-glycerol 3-phosphoethanolamine was positively correlated with the severity of BPD. There was a significant positive correlation between the abundance of Stenotrophomonas and the level of sn-glycerol 3-phosphoethanolamine.ConclusionDecreased diversity of the airway microbiome, increased abundance of Stenotrophomonas, and increased level of sn-glycerol 3-phosphoethanolamine may have potential as biomarkers for BPD. The occurrence and severity of BPD are closely related to Stenotrophomonas, which may influence the composition of the lower airway microbiome through its metabolite sn-glycerol 3-phosphoethanolamine, and may be the triggering factor of the disease. The causal relationship needs further study.

Dataset Information

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia.

Publications

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia.

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