Autoimmune enteropathy and hepatitis in pediatric heart transplant recipient

Pediatr Transplant. 2017 Mar;21(2). doi: 10.1111/petr.12877. Epub 2017 Jan 17.

Abstract

AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis. Transition from tacrolimus to sirolimus successfully increased T regulatory cells and resolved enteritis and hepatitis symptoms. Data support that thymectomy at <1 year of age increases risk of autoimmune disease due to abnormal immune maturation. Studies suggest that the sirolimus promotes the upregulation of the FoxP3 protein that is classically associated with Tregs. In turn, Tregs prevent the maturation of autoreactive B cells that lead to autoimmune reactions.

Keywords: T lymphocytes; autoimmune enteropathy; heart transplant; sirolimus; solid organ transplantation; thymectomy.

Publication types

  • Case Reports

MeSH terms

  • B-Lymphocytes / cytology
  • Child
  • Female
  • Forkhead Transcription Factors / metabolism
  • Heart Failure / complications*
  • Heart Failure / surgery*
  • Heart Transplantation*
  • Hepatitis / complications*
  • Humans
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / therapeutic use
  • Intestinal Mucosa / pathology
  • Polyendocrinopathies, Autoimmune / complications*
  • Sirolimus / therapeutic use
  • T-Lymphocytes / cytology
  • Tacrolimus / therapeutic use
  • Thymectomy
  • Up-Regulation

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents
  • Sirolimus
  • Tacrolimus

Supplementary concepts

  • Autoimmune enteropathy