IPEX due to an exon 7 skipping FOXP3 mutation with autoimmune diabetes mellitus cured by selective TReg cell engraftment
Copyright © 2018 Elsevier Inc. All rights reserved.
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 191(2018) vom: 14. Juni, Seite 52-58 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2018
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Case Reports Journal Article Research Support, Non-U.S. Gov't Autoimmune diabetes mellitus FOXP3 HSCT IPEX Splice site mutation T(Reg) FOXP3 protein, human |
| Résumé: | Copyright © 2018 Elsevier Inc. All rights reserved. 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 |
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| Description: | Date Completed 05.07.2019 Date Revised 05.07.2019 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2018.03.008 |