Reduced Humoral Immune Response to Measles and Rubella Vaccination in Children with Congenital Heart Disease Following Early Heart Surgery Involving Thymic Tissue Reduction

Background: Congenital heart disease (CHD) is the most common congenital anomaly in newborns, often requiring cardiac surgery with partial or complete thymectomy to allow surgical access to the heart. With advances in care, 97% of children with CHD now survive into adulthood, increasing the importance of studying long-term treatment effects. This study aimed to assess whether previous cardiac surgery with thymectomy affects the immune response to vaccination in children with CHD.

Methods: Children with CHD attending an outpatient clinic for follow-up were eligible for this single-center observational study. Only those who underwent heart surgery with thymectomy in the first 2 years of life were included. Age-matched, healthy children with minor pediatric surgery served as controls. All participants had received at least two measles, mumps, and rubella (MMR) vaccinations and had no known genetic disorders or immunodeficiencies. Plasma samples were collected and stored at −80°C. Anti-measles IgG and anti-rubella IgG levels were measured semiquantitatively by using a chemiluminescence assay, with a positive antibody response defined as Rubella IgG ≥10 IU/mL and Measles ≥16.5 AU/mL.

Results: A total of 35 children (mean age 8.3 years) with various forms of CHD (TAPVR, TGA, VSD, TOF, DORV) and no accompanying syndromes or known immune disorders, and 17 controls (mean age 6.8 years) were included. The mean time since the last MMR vaccination was 6.3 years for the CHD group and 6 years for controls. Children with CHD had a significantly reduced qualitative antibody response to rubella vaccination compared with controls (37% vs. 5 %, p = 0.04). Similarly, median rubella IgG titer was lower in the CHD group (16.7 vs. 25.9 IU/mL, p = 0.03). Although children with CHD also exhibited a reduced qualitative immune response to measles vaccination compared with controls (37% vs. 18%, p = 0.27), this difference was not statistically significant. Median measles IgG titer was likewise lower in the CHD group (50.8 vs. 111 AU/mL, p = 0.27), but not significant. No correlation was observed between the age at cardiac surgery and the immune response to vaccination.

Conclusion: Children with CHD who undergo cardiac surgery with thymectomy early in life demonstrate a reduced or faster waning humoral immune response to measles and rubella vaccines. Further studies are needed to investigate the impact of thymectomy and other factors such as genetics, environment, or medical treatment. While the timing of cardiac surgery does not seem to predict the immune response, individualized immunosurveillance may be warranted.

Publication History

Article published online:
11 February 2025