MHH study investigates the effect of thymus removal on the immune system in children after heart surgery and aims to create a data basis for new therapy and prevention strategies.
Tracking down the effects of thymus removal in paediatric heart surgery: Associate Professor Dr Martin Böhne. Copyright: Karin Kaiser / MHH
Many children with congenital heart defects often require heart surgery in the neonatal or infant period. A good overview and safe access are extremely important for a successful operation in view of the small size of the body and organs. The tissue between the heart and the sternum is therefore dissected and the thymus, an important part of the immune system located behind the sternum, is also partially or completely removed. This so-called thymectomy has been considered harmless over the last few decades, as earlier studies were unable to identify any clinical effects. New scientific studies using modern examination methods are now to investigate the short or long-term effects of a partial or complete thymectomy on the immune system in these children. It is largely unclear how a thymectomy alters early childhood maturation processes and the immune system's ability to react, such as the formation of antibodies after infections or vaccinations.
A research team led by Associate Professor Dr Martin Böhne, senior physician at the Department of Paediatric Cardiology and Intensive Care Medicine at Hannover Medical School (MHH), in cooperation with Professor Sarina Ravens PhD from the MHH Institute of Immunology, wants to determine the immune maturation and immune competence of affected children and identify risk groups in which thymus removal could lead to a less effective immune system later in life. In this way, the researchers want to create a data basis for new treatment and prevention strategies. The German Children's Heart Centres "Kinderherzen" funding association is supporting the project over two and a half years with around 240,000 euros.
Effects probably particularly large in newborns
"The thymus is the central organ for the formation and maturation of certain white defence cells, the so-called T lymphocytes," says Dr Böhne. In more recent studies, there are initial indications that thymectomy may increase the risk of infections, autoimmune diseases, hypothyroidism, type 1 diabetes mellitus, cancer and bronchial asthma in adolescence and adulthood. "Until a few years ago, the aim was for children with severe heart defects to survive at all," explains the senior physician. Today, the majority of children with congenital heart defects reach adulthood. "We therefore have to address the question of how we can improve the quality of life, not least due to significantly improved examination methods."
Significant effects are expected due to thymus removal, especially in newborns and infants. This is because their immune system develops primarily after birth, when it comes to terms with the new environment and thus forms an immunological memory. "In this sensitive phase, the normal maturation and adaptation of the immune system to environmental factors and thus the defence against pathogens could be impaired by the removal of the thymus," suspects Dr Böhne. "However, the studies published to date do not indicate whether certain changes in the immune system are dependent on the age at which the thymectomy was performed."
Investigating different age groups
In the project, the researchers are now looking in detail at T cells of the innate and acquired immune system. To do this, they are analysing the immune system of children of different age groups using a small blood sample. One group consists of older children who had their thymus removed in early childhood as part of an operation for a congenital heart defect. A second group consists of newborns, infants and young toddlers who are yet to undergo heart surgery with possible removal of the thymus. The focus here is on the immune system before the operation and in the further course of development. The researchers then compare the results with the immune status of children of the same age with healthy hearts. " In addition, we determine the antibodies produced by vaccinations in order to draw conclusions about protection against diseases in children with congenital heart defects," explains Dr Böhne.
Preventive measures for risk groups
"Through our research, we want to understand whether there are risk groups or certain heart defects in which particularly pronounced changes in the immune system occur," emphasises Dr Böhne. "We also want to determine whether and what possible effects on the immune system can be detected even after several years and whether children can build up sufficient protection against these diseases through regular vaccinations even after the thymus has been removed." The aim is to promote the development of special preventive measures for at-risk groups in order to minimise or even prevent changes in the immune system. "In the future, our findings could help to adapt the current vaccination schedule for children with congenital heart defects or to change surgical techniques towards more thymus preservation," hopes the paediatric cardiologist.
Text: Kirsten Pötzke