Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis: First human report.

Autor: Elmonem MA; Department of Pediatric Nephrology & Development and Regeneration, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.; Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt., Veys K; Department of Pediatric Nephrology & Development and Regeneration, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium., Oliveira Arcolino F; Department of Pediatric Nephrology & Development and Regeneration, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium., Van Dyck M; Department of Pediatric Nephrology & Development and Regeneration, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium., Benedetti MC; Department of Laboratories, Pathology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Diomedi-Camassei F; Department of Laboratories, Pathology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., De Hertogh G; Department of Translational Cell and Tissue Research, KU Leuven - University of Leuven, Leuven, Belgium., van den Heuvel LP; Department of Pediatric Nephrology & Development and Regeneration, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.; Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands., Renard M; Department of Pediatric Hematology and Oncology, KU Leuven - University of Leuven, Leuven, Belgium., Levtchenko E; Department of Pediatric Nephrology & Development and Regeneration, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2018 Nov; Vol. 18 (11), pp. 2823-2828. Date of Electronic Publication: 2018 Aug 21.
DOI: 10.1111/ajt.15029
Abstrakt: Cystinosis is an autosomal recessive lysosomal storage disorder characterized by the defective transport of the amino acid cystine out of the lysosome due to a deficiency of cystinosin, the lysosomal cystine transporter. Patients have lysosomal cystine accumulation in various tissues, leading to cellular stress and damage, particularly in the kidney, cornea, and other extrarenal tissues. Cysteamine, a cystine-depleting agent, improves survival and delays the progression of disease, but it does not prevent the development of either renal failure or extrarenal complications. Furthermore, the drug has severe adverse effects that significantly reduce patient compliance. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently established as a therapeutic option for many inborn errors of metabolism, where the main pathologic driving factor is an enzyme deficiency. Recent studies in the cystinosis mouse-model suggested that HSCT could be a curative treatment alternative to cysteamine therapy. We treated a 16-year-old boy who had infantile cystinosis and side effects of cysteamine therapy with HSCT. We were able to demonstrate successful transfer of the wild-type cystinosin protein and CTNS mRNA to nonhematological epithelial cells in the recipient, as well as a decrease in the tissue cystine-crystal burden. This is the first report of allogeneic HSCT in a patient with cystinosis, the prototype of lysosomal membrane-transporter disorders.
(© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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