Publication:
Hematopoietic Stem Cell Transplantation in Patients with Heterozygous STAT1 Gain-of-Function Mutation

Simple item page
dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsKiykim, Ayca; Charbonnier, Louis Marie; Akcay, Arzu; Karakoc-Aydiner, Elif; Ozen, Ahmet; Ozturk, Gulyuz; Chatila, Talal A.; Baris, Safa
dc.date.accessioned2022-03-14T10:18:26Z
dc.date.available2022-03-14T10:18:26Z
dc.date.issued2019-01
dc.description.abstractPurposeHuman signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disorder. Here, we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT.MethodsData on the HSC sources, conditioning regimen, graft-versus-host disease (GvHD) and antimicrobial prophylaxis, and the post-transplant course including engraftment, GvHD, transplant-related complications, infections, chimerism, and survival were evaluated. Pre- and post-transplant immunological studies included enumeration of circulating interferon gamma (IFN-)- and interleukin 17 (IL-17)-expressing CD4(+) T cells and analysis of IFN--induced STAT1 phosphorylation in patient 1 (P1)'s T cells.ResultsP1 was transplanted with cord blood from an HLA-identical sibling, and P2 with bone marrow from a fully matched unrelated donor using a reduced toxicity conditioning regimen. While P1 completely recovered from her disease, P2 suffered from systemic CMV disease and secondary graft failure and died due to severe pulmonary involvement and hemorrhage. The dysregulated IFN- production, suppressed IL-17 response, and enhanced STAT1 phosphorylation previously found in the CD4(+) T cells of P1 were normalized following transplantation.ConclusionHSCT could be an alternative and curative therapeutic option for selected STAT1 GOF mutant patients with progressive life-threatening disease unresponsive to conventional therapy. Morbidity and mortality-causing complications included secondary graft failure, infections, and bleeding.
dc.identifier.doi10.1007/s10875-018-0575-y
dc.identifier.eissn1573-2592
dc.identifier.issn0271-9142
dc.identifier.pubmed30543054
dc.identifier.urihttps://hdl.handle.net/11424/244331
dc.identifier.wosWOS:000458867500010
dc.language.isoeng
dc.publisherSPRINGER/PLENUM PUBLISHERS
dc.relation.ispartofJOURNAL OF CLINICAL IMMUNOLOGY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectSTAT1
dc.subjectgain-of function mutation
dc.subjectmucocutaneous candidiasis
dc.subjectautoimmunity
dc.subjecthematopoietic stem cell transplantation
dc.subjectCHRONIC MUCOCUTANEOUS CANDIDIASIS
dc.subjectSIGNAL TRANSDUCER
dc.subjectTRANSCRIPTION 1
dc.subjectORAL VALGANCICLOVIR
dc.subjectPREEMPTIVE THERAPY
dc.subjectACTIVATOR
dc.subjectRUXOLITINIB
dc.subjectUNDERLIE
dc.subjectIMMUNITY
dc.titleHematopoietic Stem Cell Transplantation in Patients with Heterozygous STAT1 Gain-of-Function Mutation
dc.typearticle
dspace.entity.typePublication
local.avesis.id0240ba9c-e21a-46e5-8233-e66a5963b5bf
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages8
local.journal.quartileQ1
oaire.citation.endPage44
oaire.citation.issue1
oaire.citation.startPage37
oaire.citation.titleJOURNAL OF CLINICAL IMMUNOLOGY
oaire.citation.volume39
relation.isAuthorOfPublication3e9c297b-e636-4836-8f61-dc9c8b7c29cf
relation.isAuthorOfPublication.latestForDiscovery3e9c297b-e636-4836-8f61-dc9c8b7c29cf

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Kiykim et al. - 2019 - Hematopoietic Stem Cell Transplantation in Patient.pdf
Size:
768.41 KB
Format:
Adobe Portable Document Format
Download

Collections

Research Outputs