title: Autoimmune enteropathy and hepatitis in pediatric heart transplant recipient.
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.
authors.affiliation: Medical University of South Carolina - MUSC, Charleston, SC, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lewis
authors.affiliation: Department of Pediatrics Cardiology, MUSC, Charleston, SC, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Butts
authors.affiliation: Department of Pediatric Gastroenterology, MUSC, Charleston, SC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Antonio Quiros
authors.affiliation: Department of Hematology/Oncology, MUSC, Charleston, SC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hudspeth
authors.affiliation: Department of Pediatric Nephrology, MUSC, Charleston, SC, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Twombley
authors.affiliation: Department of Pediatrics Cardiology, MUSC, Charleston, SC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Savage
authors.affiliation: Department of Pathology, MUSC, Charleston, SC, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Self
authors.affiliation: Department of Pediatrics Cardiology, MUSC, Charleston, SC, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Burnette
authors.affiliation: Department of Pathology, MUSC, Charleston, SC, USA.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Sun
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006333:Heart Failure / Q000150:complications* / Q000601:surgery*; D016027:Heart Transplantation; D006505:Hepatitis / Q000150:complications*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000473:pathology; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications*; D020123:Sirolimus / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology; D016559:Tacrolimus / Q000627:therapeutic use; D013934:Thymectomy; D015854:Up-Regulation
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus
keywords: T lymphocytes; autoimmune enteropathy; heart transplant; sirolimus; solid organ transplantation; thymectomy