Changes in Thymic Size and Immunity Are Associated with Bronchopulmonary Dysplasia

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Objective Preterm infants with bronchopulmonary dysplasia (BPD) are at increased risk for dysfunctional immune responses in the postnatal period. This study aimed to verify the hypothesis that thymic function is altered in infants with BPD and changes in the expression of thymic function-related genes affect thymic development.

Study Design Included in the study were infants who had a gestational age ≤32 weeks and survived to a postmenstrual age of ≥36 weeks. The clinical features and thymic size were comparatively studied between infants with and without BPD. Thymic function and the expression of thymic function-related genes were determined in BPD infants at birth, week 2, and 4 of life. The thymic size was ultrasonographically assessed in terms of the thymic index (TI) and thymic weight index (TWI). T-cell receptor excision circles (TRECs) and gene expression were quantitatively determined by real-time quantitative reverse transcription polymerase chain reaction.

Results Compared to non-BPD infants, their BPD counterparts had a shorter GA, lower birth weight, lower Apgar scores at birth, and were more likely to be of the male gender. BPD infants had an elevated incidence of respiratory distress syndrome and sepsis. TI was 1.73 ± 0.68 versus 2.87 ± 0.70 cm3 and TWI was 1.38 ± 0.45 versus 1.72 ± 0.28 cm3/kg in the BPD group versus the non-BPD group (p < 0.05). In BPD infants, no significant changes were observed in thymic size, lymphocyte counts, and TREC copy numbers at the first 2 weeks (p > 0.05), but they all exhibited a significant increase at week 4 (p < 0.05). BPD infants presented a trend toward increased expression of transforming growth factor-β1 and decreased expression of forkhead box protein 3 (Foxp3) from birth to week 4 (p < 0.05). Nonetheless, no significant difference was found in IL-2 or IL-7 expression at all time points (p > 0.05).

Conclusion For preterm infants with BPD, reduced thymic size at birth might be associated with impaired thymic function. Thymic function was developmentally regulated in the BPD process.

Key Points

For preterm infants with BPD, reduced thymic size at birth might be associated with impaired thymic.

BPD infants had an elevated incidence of respiratory distress syndrome and sepsis.

Thymic function was developmentally regulated in the BPD process.

Keywords preterm infant - bronchopulmonary dysplasia - thymic function - T-cell receptor excision circles - TGF-β signaling Ethical Approval and Consent to Participate

All methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The studies involving human participants were reviewed and approved by the Institutional Review Board of Union Hospital, Huazhong University of Science and Technology (2018), Wuhan, China. Written informed consent to participate in this study was provided by the participants' legal guardians/next of kin. Written informed consent was obtained from the individual and minors' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.


Authors' Contributions

Y.C. and Y.S. designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. H.P., C.Z., D.L., J.L., and J.T. designed the data collection instruments, collected the data, and reviewed and revised the manuscript. Y.L. designed the study, coordinated, and supervised data collection, and critically reviewed the manuscript for important intellectual content. The author(s) read and approved the final manuscript.


#These authors have contributed equally to this work.


Publication History

Received: 17 October 2022

Accepted: 04 April 2023

Article published online:
16 May 2023

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