Thymic Atrophy and Immune Dysregulation in Infants with Complex Congenital Heart Disease

Abstract

Congenital heart disease (CHD) is the most common birth defect, and up to 50% of infants with CHD require cardiovascular surgery early in life. Current clinical practice often involves thymus resection during cardiac surgery, detrimentally affecting T-cell immunity. However, epidemiological data indicate that CHD patients face an elevated risk for infections and immune-mediated diseases, independent of thymectomy. Hence, we examined whether the cardiac defect impacts thymus function in individuals with CHD. We investigated thymocyte development in 58 infants categorized by CHD complexity. To assess the relationship between CHD complexity and thymic function, we analyzed T-cell development, thymic output, and biomarkers linked to cardiac defects, stress, or inflammation. Patients with highly complex CHD exhibit thymic atrophy, resulting in low frequencies of recent thymic emigrants in peripheral blood, even prior to thymectomy. Elevated plasma cortisol levels were detected in all CHD patients, while high NT-proBNP and IL-6 levels were associated with thymic atrophy. Our findings reveal an association between complex CHD and thymic atrophy, resulting in reduced thymic output. Consequently, thymus preservation during cardiovascular surgery could significantly enhance immune function and the long-term health of CHD patients.

Effects of antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability following paediatric open-heart surgery and thymectomy: a single-centre retrospective cohort study

“…The prevalence of the complex cardiac defects such as UVH, TGA and TOF were similar between the two groups as well as the participants’ age at the time of primary operation. While we did not find differences in the severity of cardiac defects between the groups, we cannot completely exclude the possibility that the differences in later health could be affected by cardiac condition, as findings by Bremer et al 40 suggest that complex CHDs can affect the thymic function even before thymectomy. Broad-spectrum antibiotics were already more often administered in the symptomatic group before thymectomy, which could be due to immunological effects of complex CHD or an unknown malfunction of the immune system or other simultaneous comorbidities increasing the risk for immunological vulnerability.…”

“…2 3 9-11 Open access removal itself, although requiring careful assessment of the possible inherent immunological effect of complex CHDs. 40 Our findings suggest an association between selfreported immunological vulnerability and increased use of antibiotics in early childhood in thymectomised children. These findings are in accordance with recent scientific results regarding the immunological effects of early-life antibiotics in paediatric patients.…”

“… 2 3 9–11 Focusing only on children who have undergone total thymectomy could have provided more insight into the role of thymus removal itself, although requiring careful assessment of the possible inherent immunological effect of complex CHDs. 40 …”