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Atopic disorders are more common in children after heart transplant (HTx). We hypothesized that HTx at an early age and thymus excision (TE) affect development of T and B cells, especially regulatory T cells (Tregs), which help maintain tolerance.In this single-center study including 24 patients transplanted between 2013 and 2018, we investigated lymphocyte patterns in relation to these factors using flow cytometry. Clinical data were collected from standardized questionnaires and medical charts. Patients were stratified into TE and non-TE groups as well as patients with and without post-transplant atopy development/worsening.64% of TE patients experienced new or worsening asthma/eczema post-transplant compared to 20% of non-TE patients. TE patients had higher total Treg proportions (CD4+CD25+CD127lo) than non-TE patients (p = .043), but borderline significantly lower naïve Tregs (CD45RA+CD27-) (p = .057). Memory CD4+ T cells were higher in TE patients in trend (p = .084). Total Tregs did not differ between atopic/nonatopic groups, although naïve Tregs were significantly lower in atopic patients (p = .028). Memory CD4+ T cells were higher in atopic patients in trend (p = .082). IgM+IgD+ B cells were higher in nonatopic patients in trend (p = .064).New/worsening atopy is more common in thymectomized HTx children and is associated with alterations in T-cell profiles. Avoiding TE may prevent these alterations and reduce incidence of atopy post-HTx.

BACKGROUND There is limited information about HRQL after pediatric heart transplantation at a young age. METHODS Prospective follow-up study of children who received a heart transplant at age ≤4 years. HRQL was assessed using the PedsQLTM 4.0 at age 4.5 years. This cohort was compared with healthy children, children with CHD, and with chronic conditions. Peri-operative factors associated with HRQL were also explored. RESULTS Of 66 eligible patients, 15 (23%) died prior to the HRQL assessment and 2 (3%) were lost to follow-up, leaving 49 patients. Indication for transplantation was CHD in 27 (55%) and CMP in 22 (45%). Median age (IQR) at transplant was 9 (5-31) months. HRQL was significantly lower in transplanted children compared to population norms (65.3 vs 87.3, P

Urschel S, Rieck BD, Birnbaum J, Dalla Pozza R, Rieber N, Januszewska K, Fuchs A, West LJ, Netz H, Belohradsky BH. Impaired cellular immune response to diphtheria and tetanus vaccines in children after thoracic transplantation. Pediatr Transplantation 2011: 15: 272–280. © 2011 John Wiley & Sons A/S. Abstract: Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p

Children after heart transplantation are considered as at-risk patients for extracardiac atherosclerotic complications. Noninvasive ultrasound measurement of the common carotid artery (IMT) provides valid information about the endothelial structure of the vascular system. Twenty-two patients (17 male, mean age 12.4 +/- 4.5 yr) after heart and (5.7 +/- 4.5 yr) heart-lung transplantation were enrolled. The mean IMT was measured and compared with a control group (18 children, 10 male, mean age 11.8 +/- 1.8 yr) and to normative data. Transplanted children had a higher IMT than controls (0.453 +/- 0.003 vs. 0.424 +/- 0.002 mm, p < 0.001). IMT-SDS was increased as well (1.6 +/- 0.1 vs. 0.8 +/- 0, p < 0.001). Transplanted children had a higher LDL/HDL-ratio (2.2 +/- 0.2 vs. 1.2 +/- 0.1, p < 0.001). Time after transplantation, age at the time of transplantation, or medical therapy did not influence the findings. We found evidence for subclinical atherosclerosis in children after heart and heart-lung transplantation. Even if single atherosclerotic risk factors could not be identified, transplanted children seem to be at risk for atherosclerosis. Our findings support the recently published statement of the AHA-Expert panel: after heart transplantation atherosclerotic complications may occur with increased incidence. We propose the IMT-measurement in these patients as an easy method to assess the vascular status and to guide preventive measures.

Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p0.001), with more patients having protective antibody levels against diphtheria (p0.02) and tetanus (p0.001). There was no increased proliferation in non-stimulated or stimulated cultures after vaccination. The number of T-lymphocytes activated by the vaccination antigens was similar pre- and post-vaccination, whereas HLA-DR-expression on stimulated and non-stimulated CD4(+) T-cells increased significantly. Increase in antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies.

Pandemic influenza A/H1N1 virus has the potential to cause severe disease in pediatric transplant patients. A pandemic vaccine against H1N1 is effective in immunocompetent children. We investigated the immunogenicity of this vaccine when given in the first six months after heart transplantation. Four patients younger than two yr received two doses of vaccine and one patient older than seven yr received one dose. Titers were obtained using the HAI at baseline and after final immunization. Five patients were enrolled, ages 0.5-7 yr. Median age at the time of transplant was five months (range 3 wk-7 yr). All patients received induction with anti-thymoglobulin and maintenance immunosuppression with tacrolimus, MMF, and prednisone. Patients were immunized with the adjuvanted H1N1 vaccine after heart transplant at median time of nine wk (range 5-23 wk) post-transplant. Three of five developed protective titers against H1N1. A proportion of pediatric patients may respond to influenza vaccine even when immunized in the early post-transplant period.

Pandemic influenza A/H1N1 virus has the potential to cause severe disease in pediatric transplant patients. A pandemic vaccine against H1N1 is effective in immunocompetent children. We investigated the immunogenicity of this vaccine when given in the first six months after heart transplantation. Four patients younger than two yr received two doses of vaccine and one patient older than seven yr received one dose. Titers were obtained using the HAI at baseline and after final immunization. Five patients were enrolled, ages 0.5-7 yr. Median age at the time of transplant was five months (range 3 wk-7 yr). All patients received induction with anti-thymoglobulin and maintenance immunosuppression with tacrolimus, MMF, and prednisone. Patients were immunized with the adjuvanted H1N1 vaccine after heart transplant at median time of nine wk (range 5-23 wk) post-transplant. Three of five developed protective titers against H1N1. A proportion of pediatric patients may respond to influenza vaccine even when immunized in the early post-transplant period.

In the first two yr of life blood-group incompatible (ABO-incompatible) heart transplantation can be performed leading to immune tolerance to donor blood group. Antibody titers should be below 1:4. VAD use is correlated with sensitization toward blood-group antigens. A boy was diagnosed with dilated cardiomyopathy at nine months of age and listed for 0-compatible transplantation. Progressive heart failure required implantation of a left VAD. His listing was extended for ABO-incompatible transplantation despite antibody titers of 1:32 anti-A and 1:8 anti-B. After 26 days on VAD, he was transplanted with a B donor heart. No hyperacute or acute rejection occurred in 12 months post-transplant. Anti-B antibodies rose to a maximum of 1:2. No use of rituximab or plasmapheresis was required. There are no signs of graft vasculopathy. This indicates that inclusion criteria for ABO-incompatible transplantation may be extended to immediate cases. This is the first case with a healthy immune system to show signs of tolerance development after ABO-incompatible heart transplantation with increased prior antibody titers and without specific treatment.