Allergies and autoimmune disorders in children after heart transplantation

Abstract

Pediatric heart transplantation requires lifelong immune suppression and may require thymectomy, both of which alter T-cell repertoires. We hypothesized that atopic and autoimmune diseases are more common in pediatric heart transplant patients than the general population, and that transplantation in early childhood increases the risk of development or worsening of atopic or autoimmune disease. A cross-sectional single-center study including 21 heart transplant patients aged ≤18 years was conducted. Data collected included age at transplant, induction, thymectomy, and development and severity of atopic or autoimmune disease. A majority (67%) reported having any atopic disease post-transplant, all of whom reported onset or worsening post-transplantation. Thymectomized patients were significantly more likely to have asthma (P = 0.018) and report asthma worsening post-transplant (P = 0.045). Patients with worsening of asthma post-transplant were transplanted at a significantly younger age (P = 0.040). ABO incompatible and ABO compatible recipients presented similarly. Anemia was common (38%) but not always clearly of autoimmune origin. Atopic diseases are common in children following heart transplantation: Compared to the general population, there is a higher prevalence of eczema (43% vs 11%) and asthma (33% vs 9%). Both thymectomy and younger age at transplant are associated with atopic disorders, possibly due to altered T-cell repertoires.

Immune dysregulation and Th2 polarization are associated with atopic dermatitis in heart-transplant children: A delicate balance between risk of rejection or atopic symptoms

“…8,11 Early thymectomy also results in reduced TCR diversity, 12 which has been associated with AD. 1,16 In agreement with all these findings, our results indicate that age at time of heart transplantation and subsequent thymectomy seems to be a crucial factor for AD development, as patients who developed AD had been transplanted at younger ages than non-AD patients. 1,16 In agreement with all these findings, our results indicate that age at time of heart transplantation and subsequent thymectomy seems to be a crucial factor for AD development, as patients who developed AD had been transplanted at younger ages than non-AD patients.…”

“…13 The impaired thymic function has also been related to a higher incidence of autoimmune and atopic diseases, as shown in children with thymic hypoplasia secondary to partial Di-George syndrome, 14,15 and even in pediatric heart transplant patients. 1,16 In agreement with all these findings, our results indicate that age at time of heart transplantation and subsequent thymectomy seems to be a crucial factor for AD development, as patients who developed AD had been transplanted at younger ages than non-AD patients.…”

“…Therefore, high eosinophil counts, as observed in our AD cohort, has been associated with an absence of rejection in heart-transplant pediatric recipients, 28 strengthening the association between eosinophilia, AD development, and freedom from rejection.Another interesting point discovered by our work was the presence of higher counts of Tregs with an effector phenotype (effector memory and TemRA) in AD patients. Summing up, the younger age at transplantation and subsequent thymectomy, the dominance of a Th2 response, and an apparent inability of Treg cells to prevent a Th1/Th2 imbalance could constitute the main mechanisms responsible for the onset of AD in heart-transplant children that has been reported by several authors 1,16. Therefore, even if Treg cells appear to be exhausted and unable to control Th2 expansion at the time of this study (>4 years posttransplant), it is possible that F I G U R E 3 Association loss between Treg and IL-4-secreting CD4+ T cells in AD patients.…”

Management and Outcomes of Immune Cytopenia Following Pediatric Heart Transplantation

“…Autoimmune cytopenias (AICs), such as autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenia (AITP), and autoimmune neutropenia (AIN), are known potential complications following pediatric solid organ transplantation (SOT) [1]. These have been shown to be linked to a variety of factors, including infections, ABO incompatibility, and immune dysregulation [1,2]. AICs can be difficult to treat, particularly in children.…”

“…AICs can be difficult to treat, particularly in children. Prior studies have asserted that the prolonged use of immunosuppressive medications (ISMs) to prevent allograft rejection in SOT patients may be responsible for the development of immune cytopenias [1]. In addition, the higher levels of immunosuppression often required for cardiac transplant recipients [2], predispose them to a higher incidence of cytopenias at a relatively younger age than liver or kidney transplant patients [3].…”