IPEX due to an exon 7 skipping FOXP3 mutation with autoimmune diabetes mellitus cured by selective TReg cell engraftment.
Clin Immunol
; 191: 52-58, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29567430
ABSTRACT
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare inherited disorder leading to severe organ-specific autoimmunity. IPEX is caused by hemizygous mutations in FOXP3, which codes for a master transcription factor of regulatory T (TReg) cell development and function. We describe a four-year-old boy with typical but slightly delayed-onset of IPEX with autoimmune diabetes mellitus, enteropathy, hepatitis and skin disease. We found the unreported FOXP3 splice site mutation c.816+2T>A that leads to the loss of leucine-zipper coding exon 7. RNA-Seq revealed that FOXP3Δ7 leads to differential expression of FOXP3 regulated genes. After myeloablative conditioning the patient underwent allogeneic HSCT from a matched unrelated donor. HSCT led to the resolution of all IPEX symptoms including insulin requirement despite persisting autoantibody levels. After initial full donor engraftment nearly complete autologous reconstitution was documented, but donor-derived TReg cells persisted with a lineage-specific chimerism of >70% and the patient remained in clinical remission.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Éxons
/
Linfócitos T Reguladores
/
Transplante de Células-Tronco Hematopoéticas
/
Doenças Genéticas Ligadas ao Cromossomo X
/
Diabetes Mellitus Tipo 1
/
Diarreia
/
Fatores de Transcrição Forkhead
/
Doenças do Sistema Imunitário
/
Mutação
Limite:
Child, preschool
/
Humans
/
Male
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha