Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engr...

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Bibliographic Details
Published in:Pediatric transplantation 2014-02, Vol.18 (1), p.E25-E30
Main Authors: Horino, Satoshi, Sasahara, Yoji, Sato, Miki, Niizuma, Hidetaka, Kumaki, Satoru, Abukawa, Daiki, Sato, Atsushi, Imaizumi, Masue, Kanegane, Hirokazu, Kamachi, Yoshiro, Sasaki, Shinya, Terui, Kiminori, Ito, Etsuro, Kobayashi, Ichiro, Ariga, Tadashi, Tsuchiya, Shigeru, Kure, Shigeo
Format: Article
Language:English
Subjects:
allogeneic hematopoietic stem cell transplantation
Bone Marrow Transplantation
Child
Diabetes Mellitus, Type 1 - congenital
Diarrhea
enteropathy
Forkhead box protein 3
Gastrointestinal Diseases - pathology
Genetic Diseases, X-Linked - blood
Genetic Diseases, X-Linked - immunology
Genetic Diseases, X-Linked - therapy
Humans
immune dysregulation
Immune System Diseases - congenital
Male
polyendocrinopathy
reduced intensity conditioning
regulatory T cells
T-Lymphocytes, Regulatory - immunology
Transplantation, Homologous
X-linked syndrome
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Summary:IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.
ISSN:1397-3142
1399-3046
DOI:10.1111/petr.12184