Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants

Pagel, Julia; Twisselmann, Nele; Rausch, Tanja K.; Waschina, Silvio; Hartz, Annika; Steinbeis, Magdalena; Olbertz, Jonathan; Nagel, Kathrin; Steinmetz, Alena; Faust, Kirstin; Demmert, Martin; Göpel, Wolfgang; Herting, Egbert; Rupp, Jan; Härtel, Christoph

doi:10.3389/fimmu.2020.565257

Cited by 29 publications

(26 citation statements)

References 62 publications

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“…For example, the influence of sex differences, birth weight, fetal growth restriction, and exposure to antenatal corticosteroids on miRNA profile changes were not directly evaluated. Third, given that we studied preterm neonates of different developmental trajectories, it is possible that the differences we noted in the miRNA expression may reflect changes in cell populations present in the TA [79,80]. Lastly, it is becoming evident in recent studies that the microbiota in TAs can affect miRNA expression [81,82].…”

Section: Discussionmentioning

confidence: 95%

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

Siddaiah¹,

Oji‐Mmuo²,

Montes³

et al. 2021

Preprint

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Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth and arrested fetal lung development. The incidence of BPD remains on the rise, as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of severe BPD. We collected tracheal aspirates (TA) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, FDR &lt; 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD vs. the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extreme premature infants contain miRNA signatures associated with severe BPD. These signatures may serve as biomarkers of disease severity in infants with BPD.

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Section: Discussionmentioning

confidence: 95%

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

Siddaiah¹,

Oji‐Mmuo²,

Montes³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…For example, the influence of sex differences, birth weight, fetal growth restriction, and exposure to antenatal corticosteroids on miRNA profile changes was not directly evaluated. Third, given that we studied preterm neonates of different developmental trajectories, it is possible that the differences we noted in the miRNA expression may reflect changes in cell populations present in the TA [ 88 , 89 ]. Lastly, it is becoming evident in recent studies that the microbiota in TAs can affect miRNA expression [ 90 , 91 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants

et al. 2021

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Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.

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“…Cut off of Treg level in normal preterm was 8.97 (range 7.25-10.07) and outside the range considered dysregulation. 15 The diagnosis of RDS was established based on the existing signs and symptoms, including tachypnea (respiratory rate of > 60 times/minute), nasal flaring, central cyanosis, and radiological findings of ground glass appearance. Neonates with RDS were evaluated until the end of the observation period.…”

Section: Methodsmentioning

confidence: 99%

Vitamin D and T- regulator cells are not independent factors for RDS in premature neonates

Marsubrin¹,

Firmansyah²,

Rohsiswatmo³

et al. 2021

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Background The high morbidity and mortality of premature neonates remain significant problem in Indonesia with respiratory distress syndrome (RDS) as one of the most common problem. Vitamin D plays an important role in lung maturity. Vitamin D deficiency causes epithelial cell inflammation, leading to a higher risk of RDS. Previous studies suggest that T regulatory cells (Treg) in inflammatory diseases, such as RDS in neonates, are possibly linked to vitamin D deficiency. Objective To determine the role of vitamin D on RDS and Treg cells in very premature or very low birth weight neonates. Methods A prospective cohort study conducted on premature neonates in Neonatology Division, Department of Child Health, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Umbilical cord blood samples were collected to evaluate total vitamin D 25-OH levels and Treg cells. Subjects with RDS were evaluated until the end of the observation period. Results The mean umbilical cord vitamin D level was 15.79 (SD 6.9) ng/mL, and 53% of the subjects were found to be deficient. As much as 65.1% of neonates had RDS. The mean Treg level was 11.38 (SD 2.45)%. No significant correlation was observed between vitamin D level and the occurrence of RDS (RR 0.87; 95%CI 0.56 to 1.34; P=0.53); vitamin D level and the dysregulation of Treg cells (RR 1.30; 95%CI 0.76 to 2.21; P=0.31) as well as between Treg dysregulation and RDS (RR 1.11; 95%CI 0.70 to 1.75; P=0.64). However, we found that RDS group had a lower gestational age and higher presentation of dysregulation Treg. Conclusion In very premature or very low birth weight neonates, no association between occurence of RDS and vitamin D deficiency as well as Treg cell dysregulation.

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Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants

Cited by 29 publications

References 62 publications

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

Tracheal Aspirate miRNA Signatures in Preterm Infants with Severe Bronchopulmonary Dysplasia

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants

Vitamin D and T- regulator cells are not independent factors for RDS in premature neonates

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