Hematopoietic Stem Cell Transplantation Resolves the Immune Deficit Associated with STAT3-Dominant-Negative Hyper-IgE Syndrome

Stephanie C. Harrison, Christo Tsilifis, Mary A. Slatter, Zohreh Nademi, Austen Worth, Paul Veys, Mark J. Ponsford, Stephen Jolles, Waleed Al-Herz, Terence Flood, Andrew J. Cant, Rainer Doffinger, Gabriela Barcenas-Morales, Ben Carpenter, Rachael Hough, Ásgeir Haraldsson, Jennifer Heimall, Bodo Grimbacher, Mario Abinun, Andrew R. Gennery*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
5 Downloads (Pure)

Abstract

Autosomal dominant hyper-IgE syndrome caused by dominant-negative loss-of-function mutations in signal transducer and activator of transcription factor 3 (STAT3) (STAT3-HIES) is a rare primary immunodeficiency with multisystem pathology. The quality of life in patients with STAT3-HIES is determined by not only the progressive, life-limiting pulmonary disease, but also significant skin disease including recurrent infections and abscesses requiring surgery. Our early report indicated that hematopoietic stem cell transplantation might not be effective in patients with STAT3-HIES, although a few subsequent reports have reported successful outcomes. We update on progress of our patient now with over 18 years of follow-up and report on an additional seven cases, all of whom have survived despite demonstrating significant disease-related pathology prior to transplant. We conclude that effective cure of the immunological aspects of the disease and stabilization of even severe lung involvement may be achieved by allogeneic hematopoietic stem cell transplantation. Recurrent skin infections and abscesses may be abolished. Donor TH17 cells may produce comparable levels of IL17A to healthy controls. The future challenge will be to determine which patients should best be offered this treatment and at what point in their disease history.

Original languageEnglish
Pages (from-to)934-943
Number of pages10
JournalJournal of Clinical Immunology
Volume41
Issue number5
DOIs
Publication statusPublished - 1 Feb 2021

Bibliographical note

CT is supported by The Job Research Foundation.

MJP is supported by the Welsh Clinical Academic Training (WCAT) programme and is a participant in the NIH Graduate Partnership Program.

BG receives support through the Deutsche Forschungsgemeinschaft (DFG) SFB1160/2_B5, under Germany’s Excellence Strategy (CIBSS—EXC-2189—Project ID 390939984, and RESIST—EXC 2155—Project ID 390874280); through the E-rare program of the EU, managed by the DFG, grant code GR1617/14-1/iPAD, and through the “Netzwerke Seltener Erkrankungen” of the German Ministry of Education and Research (BMBF), grant code: GAIN_ 01GM1910A. This work was supported in part by the Center for Chronic Immunodeficiency (CCI), Freiburg Center for Rare Diseases (FZSE).

Publisher Copyright:
© 2021, The Author(s).

Other keywords

  • Autosomal dominant hyper IgE syndrome
  • dominant-negative STAT3 mutations
  • hematopoietic stem cell transplantation
  • Job syndrome
  • STAT3-HIES T17 cells

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