Immune Dysregulation after Pediatric Heart Transplantation.

PURPOSE: There has been greater recognition of allergy and autoimmune disease in pediatric solid organ transplantation, however, their relationship with pediatric heart transplant is unclear. The purpose of this study was to explore post heart transplant immune dysregulation.

METHODS: Retrospective chart review was carried out at a single center on children less than 18 years of age, transplanted between 2000 and 2018, who were at least 1 year post heart transplant without any history of immune dysregulation before transplant.

RESULTS: Of 94 patients screened, 90 (38 males, 42.2%) met inclusion criteria. Mean age at transplant was 2.5 years (± 3.6 years) and patients were followed for a mean of 9.2 years (± 5.1 years) post-transplant. Forty-eight (53.3%) patients had a diagnosis of CHD while the remaining 42 (46.7%) had a cardiomyopathy. Immunosuppression was per institutional protocol with 85 (94.4%) patients on tacrolimus, 53 (58.8%) on MMF, 7 (7.8%) on sirolimus, 2 (2.2%) on cyclosporine, and 2 (2.2%) on maintenance prednisone. Ten (11.1%) patients had a history of oral thrush and 14 (15.6%) had other candida infections post-transplant. A need for frequent antibiotics, described as two or more in one-year, was seen in 58 (64.4%) patients. Sixteen (17.8%) patients developed adenovirus infection post-transplant. A positive PCR for CMV at any point post-transplant was found in 22 (24.4%) patients and for EBV in 49 (54.4%) patients. Of the 90 patients, 53 (58.9%) were found to develop post-transplant immune dysregulation. A total of 12 (22.6%) patients developed severe eczema and 25 (47.2%) developed new allergies to foods, medications, animals, environmental allergens and atopic reactions such as eosinophilic esophagitis. New autoimmune diseases developed in 18 (34%) patients and included cytopenias, colitis, psoriasis, uveitis, ITP, diabetes and Familial Mediterranean Fever. Eighty-five patients had detailed T-cell immunophenotyping which revealed abnormalities in CD3+CD4+ counts in 48 (56.5%) patients. Seventy-three patients also had differential data revealing low lymphocyte counts in 9 (12.3%) patients.

CONCLUSION: Allergy and autoimmune disease are common post pediatric heart transplant and are an important cause of long-term morbidity. Further study is required to better understand the pathophysiologic mechanisms behind this and to identify potential treatment or preventative strategies.