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

dc.contributor.authorKiykim, Ayca
dc.contributor.authorCharbonnier, Louis Marie
dc.contributor.authorAkcay, Arzu
dc.contributor.authorKarakoc-Aydiner, Elif
dc.contributor.authorOzen, Ahmet
dc.contributor.authorOzturk, Gulyuz
dc.contributor.authorChatila, Talal A.
dc.contributor.authorBaris, Safa
dc.date.accessioned2023-02-21T12:38:35Z
dc.date.available2023-02-21T12:38:35Z
dc.date.issued2019-01-01
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.description.issue1
dc.description.issueJAN
dc.description.pages37-44
dc.description.volume39
dc.identifier.doi10.1007/s10875-018-0575-y
dc.identifier.urihttps://hdl.handle.net/11443/2401
dc.identifier.urihttp://dx.doi.org/10.1007/s10875-018-0575-y
dc.identifier.wosWOS:000458867500010
dc.publisherSPRINGER/PLENUM PUBLISHERS
dc.relation.ispartofJOURNAL OF CLINICAL IMMUNOLOGY
dc.subjectSTAT1
dc.subjectgain-of function mutation
dc.subjectmucocutaneous candidiasis
dc.subjectautoimmunity
dc.subjecthematopoietic stem cell transplantation
dc.titleHematopoietic Stem Cell Transplantation in Patients with Heterozygous STAT1 Gain-of-Function Mutation
dc.typeArticle

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