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Published on: August 7, 2017
Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia
Soumyaroop Bhattacharya1, Jared A Mereness1, Andrea M Baran2
1Division of Neonatology, Department of Pediatrics, University of Rochester, Rochester, NY, United States.
Insights
Researchers identified gene expression patterns in CD8+ T cells to predict Bronchopulmonary Dysplasia (BPD) and Post-Prematurity Respiratory Disease (PRD) in infants. These findings offer potential biomarkers for respiratory outcomes in premature infants.
Area of Science:
- Immunology and Respiratory Medicine
- Genomics and Transcriptomics
- Neonatal and Perinatal Medicine
Background:
- Premature infants often develop Bronchopulmonary Dysplasia (BPD) and Post-Prematurity Respiratory Disease (PRD), characterized by persistent respiratory symptoms.
- Inflammation and viral infections are frequently implicated in the pathogenesis of these conditions.
- Understanding the molecular underpinnings of BPD and PRD is crucial for developing targeted interventions.
Purpose of the Study:
- To identify gene expression patterns in CD8+ T cells associated with Bronchopulmonary Dysplasia (BPD) in extremely premature infants.
- To discover molecular markers that predict the development of BPD and Post-Prematurity Respiratory Disease (PRD).
- To investigate the role of specific signaling pathways, such as TGFB, NRF2, HIPPO, and CD40, in BPD pathogenesis.
Main Methods:
- Transcriptomic profiling (RNA-Seq) of sorted peripheral blood CD8+ T cells from preterm and full-term infants.
- Analysis of gene expression data to identify outcome-related patterns and predictor gene sets for BPD and PRD.
- Statistical methods to adjust for gestational age at birth and identify differentially expressed genes and pathways.
Main Results:
- A set of 92 genes was identified that could predict BPD with moderate to high accuracy in high-risk preterm infants.
- Dysregulation of TGFB, NRF2, HIPPO, and CD40-associated pathways was consistently observed in BPD.
- A 28-gene set, involving TGFB signaling, predicted PRD status in both preterm and full-term infants.
Conclusions:
- Transcriptomic analysis of CD8+ T cells reveals molecular markers of inflammation associated with BPD and PRD.
- Specific gene sets and pathways can serve as predictors for respiratory disease development in infants.
- These findings may contribute to early identification and management strategies for respiratory complications in premature infants.
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.

