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

Satoshi Horino, Yoji Sasahara, Miki Sato, Hidetaka Niizuma, Satoru Kumaki, Daiki Abukawa, Atsushi Sato, Masue Imaizumi, Hirokazu Kanegane, Yoshiro Kamachi, Shinya Sasaki, Kiminori Terui, Etsuro Ito, Ichiro Kobayashi, Tadashi Ariga, Shigeru Tsuchiya, Shigeo Kure

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17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)E25-E30
JournalPediatric Transplantation
Volume18
Issue number1
DOIs
Publication statusPublished - 2014 Feb

Keywords

  • Forkhead box protein 3
  • X-linked syndrome
  • allogeneic hematopoietic stem cell transplantation
  • enteropathy
  • immune dysregulation
  • polyendocrinopathy
  • reduced intensity conditioning
  • regulatory T cells

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Transplantation

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    Horino, S., Sasahara, Y., Sato, M., Niizuma, H., Kumaki, S., Abukawa, D., Sato, A., Imaizumi, M., Kanegane, H., Kamachi, Y., Sasaki, S., Terui, K., Ito, E., Kobayashi, I., Ariga, T., Tsuchiya, S., & Kure, S. (2014). Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome. Pediatric Transplantation, 18(1), E25-E30. https://doi.org/10.1111/petr.12184