Impaired Early T-Cell Development in Infants with Complex Congenital Heart Disease

Background: Congenital heart disease (CHD) is the most common birth defect worldwide affecting approximately 1% of newborns. Patients with CHD are prone to infections, especially respiratory tract infections and suffer from higher hospitalization rates and mortality. Recently, it was shown that newborns with CHD display lower T-cell receptor excision circle (TREC) levels, a marker for T-cell maturation in the thymus, compared with the general population. Therefore, we hypothesize that congenital heart disease negatively affects early T cell development, probably before birth, with possible long-term consequences for the health of CHD patients.

Method: We investigated the immune and clinical profile in a cohort of 44 CHD patients who underwent thymectomy in the first year of life during heart surgery. Patients were categorized according to the complexity of their CHD. For our immunological studies we have established a comprehensive flow cytometry based single cell immunophenotyping approach to analyze 14 different maturation stages of T-cell precursors in the thymus (thymocytes). Cardiac biomarkers (e.g., troponin T, NT-proBNP) and plasma cortisol levels were compared among different cardiac conditions and correlated to the cellular composition of the thymus.

Results: Our analysis revealed a unique thymocyte signature in CHD patients less than 1 month of age who suffered from the more complex CHD (transposition of the great arteries, hypoplastic left heart syndrome/aortic stenosis/interrupted aortic arch). We found lower frequencies of the more immature double-positive (CD4+ CD8+) thymocytes, indicative of thymic stress. NT-proBNP and Troponin T correlated negatively with the frequency of double-positive cells. Moreover, we could show that patients with CHD had increased serum cortisol levels compared with age-matched healthy controls but there was no association between cortisol levels and CHD severity.

Conclusion: Abnormal thymocyte composition is associated with CHD complexity indicating that CHD by itself might lead to an impaired immune development. Further studies are needed to investigate whether these immunological alterations are transient or if there is a causal connection of CHD and immune deviations that might lead to an increased risk of developing immune mediated diseases.

Die Autoren geben an, dass kein Interessenkonflikt besteht.

Publikationsverlauf

Artikel online veröffentlicht:
03. Februar 2022