Published online March 3, 2008
PEDIATRICS Vol. 121 No. 4 April 2008, pp. e998-e1002 (doi:10.1542/peds.2007-1863)
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EXPERIENCE & REASON

Immune Reconstitution and Recovery of FOXP3 (Forkhead Box P3)-Expressing T Cells After Transplantation for IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked) Syndrome

Hong Zhan, MD, PhDa, Jo Sinclair, MSca, Stuart Adams, PhDb, Catherine M. Cale, MB, BS, PhDb, Simon Murch, MB, BSc, Lucia Perroni, PhDd, Graham Davies, MB, BChirb, Persis Amrolia, MB, BS, PhDa,b and Waseem Qasim, MB, BS, PhDa,b

a Institute of Child Health
b Great Ormond Street Hospital, London, United Kingdom
c Warwick Medical School, Coventry, United Kingdom
d Lucia Perroni, Human Genetics, Galliera Hospital, Genova, Italy

ABSTRACT

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is a rare X-linked disorder that usually presents in early childhood with immune enteropathy, diabetes mellitus, and other autoimmune complications. The disease is caused by mutations in the forkhead box P3 gene, a transcription factor that is essential for the development and function of regulatory T cells. This population of cells plays an essential role in controlling immune responses and preventing autoimmunity. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is often initially treated with immunosuppressive drugs, but only allogeneic hematopoietic stem cell transplantation has offered the possibility of cure. We recently performed an unrelated donor transplant in a child with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome by using a reduced-intensity conditioning regimen. This transplant provided a rare opportunity to gain valuable insight into the regeneration of the immune system after transplantation. Clinical recovery was associated with the emergence of regulatory T cell populations, the majority of which expressed memory phenotype markers and raised important questions about the origin and longevity of the FOXP3+ regulatory T cell pool.

Key Words: IPEX syndrome • immune dysregulation • polyendocrinopathy • enteropathy • X-linked syndrome • regulatory T cells • Tregs • forkhead box P3 • FOXP3 • reduced-intensity conditioning

Abbreviations: IPEX, immune dysregulation, polyendocrinopathy, enteropathy, X-linked • FOXP3, forkhead box P3 • Tregs, regulatory T cells • HSCT, hematopoietic stem cell transplantation • PCR, polymerase chain reaction • GvHD, graft-versus-host disease • PHA, phytohemagglutinin • Ig, immunoglobulin • TREC, T-cell receptor excision circle

Accepted Aug 30, 2007.