Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations

Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations

Author Miot, Charline Google Scholar
Imai, Kohsuke Google Scholar
Imai, Chihaya Google Scholar
Mancini, Anthony J. Google Scholar
Kucuk, Zeynep Yesim Google Scholar
Kawai, Tokomki Google Scholar
Nishikomori, Ryuta Google Scholar
Ito, Etsuro Google Scholar
Pellier, Isabelle Google Scholar
Girod, Sophie Dupuis Google Scholar
Rosain, Jeremie Google Scholar
Sasaki, Shinya Google Scholar
Chandrakasan, Shanmuganathan Google Scholar
Schmid, Jana Pachlopnik Google Scholar
Okano, Tsubasa Google Scholar
Colin, Estelle Google Scholar
Olaya-Vargas, Alberto Google Scholar
Yamazaki-Nakashimada, Marco Google Scholar
Qasim, Waseem Google Scholar
Espinosa Padilla, Sara Google Scholar
Jones, Andrea Google Scholar
Krol, Alfons Google Scholar
Cole, Nyree Google Scholar
Jolles, Stephen Google Scholar
Bleesing, Jack Google Scholar
Vraetz, Thomas Google Scholar
Gennery, Andrew R. Google Scholar
Abinun, Mario Google Scholar
Gungor, Tayfun Google Scholar
Costa-Carvalho, Beatriz Autor UNIFESP Google Scholar
Condino-Neto, Antonio Autor UNIFESP Google Scholar
Veys, Paul Google Scholar
Holland, Steven M. Google Scholar
Uzel, Gulbu Google Scholar
Moshous, Despina Google Scholar
Neven, Benedicte Google Scholar
Blanche, Stephane Google Scholar
Ehl, Stephan Google Scholar
Doffinger, Rainer Google Scholar
Patel, Smita Y. Google Scholar
Puel, Anne Google Scholar
Bustamante, Jacinta Google Scholar
Gelfand, Erwin W. Google Scholar
Casanova, Jean-Laurent Google Scholar
Orange, Jordan S. Google Scholar
Picard, Capucine Google Scholar
Abstract X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor kappa B essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftmentwas documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlyingmutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.
xmlui.dri2xhtml.METS-1.0.item-coverage Washington
Language English
Sponsor St. Giles Foundation
Rockefeller University
INSERM
Paris Descartes University
Centre de Reference des Deficits Immunitaires Hereditaires (CEREDIH)
German Ministry for Education and Research
National Institute for Health Research and GOSH Biomedical Research Centre
Robert A. Good/Jeffrey Modell Fellowship
Date 2017
Published in Blood. Washington, v. 130, n. 12, p. 1456-1467, 2017.
ISSN 0006-4971 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Hematology
Extent 1456-1467
Origin http://dx.doi.org/10.1182/blood-2017-03-771600
Access rights Closed access
Type Article
Web of Science ID WOS:000411319700012
URI https://repositorio.unifesp.br/handle/11600/57349

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