Clinical and Immunological Consequences of Early-life Thymectomy in Children with Congenital Heart Disease

Background: Congenital heart disease (CHD) is the most common birth defect worldwide. Depending on complexity of the CHD, around 50% of these children require cardiovascular surgery, which may involve removal of the thymus for a better access to the heart. Given the pivotal role of the thymus in shaping a functional adaptive immune response, thymectomy may have detrimental health consequences.

Methods: We clinically and immunologically characterized 17 children (23% female, 77% male), aged 3 to 5 years, with CHD who had undergone thymectomy in their first year of life. Of these, 65% had acyanotic CHD, and 35% cyanotic CHD. Our assessment encompassed physical and laboratory examinations, including total blood count, analysis of cardiac biomarkers and cytokine plasma levels, comprehensive immunophenotyping and a questionnaire to evaluate the frequency of infections and immune-mediated diseases. Additionally, we assessed CMV and EBV seropositivity and to test for early markers of allergy and autoimmunity we measured IgE and autoantibody levels. Finally, we analyzed the patients’ thymic output by investigating TREC numbers and recent thymic emigrants.

Results: Our study shows that thymectomized children commonly exhibit lymphopenia accompanied by an altered T cell profile. These changes include a decrease of naïve CD4 and CD8 cells, concomitant with an elevated percentage of memory T cells. We observed a significantly increased percentage of Tfh and CCR4+ CD4 cells among thymectomized children. Additionally, irrespective of CMV infection status, thymectomized children exhibit an increased percentage of exhausted PD1+ T cells. Half of the children in our study displayed low TREC numbers. Analysis of plasma cytokines relevant for homeostatic T cell proliferation revealed significantly reduced IL-15 levels in thymectomized children. We found elevated IgE levels in 19% of study participants but no relevant autoantibody titers could be detected in thymectomized children.

Conclusion: Our research reveals the immediate immunological impact of thymectomy in early-life, including premature immune aging, reduced thymic output, and signs of lymphopenia-induced T cell proliferation, potentially elevating the risk of autoimmune development later in life. These observations underscore the importance of monitoring the long-term consequences of early-life thymectomy. This work was supported by the YAEL Foundation and by the German Heart Foundation.

Publication History

Article published online:
13 February 2024