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

Lookup NU author(s): Dr Christo Tsilifis, Dr Mary Slatter, Dr Zohreh Nademi, Dr Terence Flood, Professor Andrew Cant, Dr Mario Abinun, Professor Andrew Gennery

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.


Publication metadata

Author(s): Harrison SC, Tsilifis C, Slatter MA, Nademi Z, Worth A, Veys P, Ponsford MJ, Jolles S, Al-Herz W, Flood T, Cant AJ, Doffinger R, Barcenas-Morales G, Carpenter B, Hough R, Haraldsson Á, Heimall J, Grimbacher B, Abinun M, Gennery AR

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Immunology

Year: 2021

Pages: Epub ahead of print

Online publication date: 01/02/2021

Acceptance date: 13/01/2021

Date deposited: 03/02/2021

ISSN (print): 0271-9142

ISSN (electronic): 1573-2592

Publisher: Springer

URL: https://doi.org/10.1007/s10875-021-00971-2

DOI: 10.1007/s10875-021-00971-2

PubMed id: 33523338


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