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

  • Ayca Kiykim
  • Louis Marie Charbonnier
  • Arzu AkcayEmail author
  • Elif Karakoc-Aydiner
  • Ahmet Ozen
  • Gulyuz Ozturk
  • Talal A. Chatila
  • Safa BarisEmail author
Original Article



Human 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.


Data 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-γ)- and interleukin 17 (IL-17)-expressing CD4+ T cells and analysis of IFN-β-induced STAT1 phosphorylation in patient 1 (P1)’s T cells.


P1 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-γ production, suppressed IL-17 response, and enhanced STAT1 phosphorylation previously found in the CD4+ T cells of P1 were normalized following transplantation.


HSCT 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.


STAT1 gain-of function mutation mucocutaneous candidiasis autoimmunity hematopoietic stem cell transplantation 



This manuscript is dedicated to the memory of Professor Dr. Isil Berat Barlan (1958-2015). This work was supported by the National Institutes of Health (5R01AI065617) to T.A.C and a grant from the Scientific and Technological Research Council of Turkey (1059B191401284) to S.B.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ayca Kiykim
    • 1
  • Louis Marie Charbonnier
    • 2
  • Arzu Akcay
    • 3
    Email author
  • Elif Karakoc-Aydiner
    • 1
  • Ahmet Ozen
    • 1
  • Gulyuz Ozturk
    • 3
  • Talal A. Chatila
    • 2
  • Safa Baris
    • 1
    Email author
  1. 1.Division of Pediatric Allergy/ImmunologyMarmara UniversityIstanbulTurkey
  2. 2.Division of Immunology, Boston Children’s Hospital and Department of PediatricsHarvard Medical SchoolBostonUSA
  3. 3.Acıbadem Atakent Hospital, Pediatric Bone Marrow Transplantation UnitAcibadem UniversityIstanbulTurkey

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