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Lookup NU author(s): Rebecca Walsh, Dr Zohreh Nademi, Dr Alexandra Laberko, Dr Terence Flood, Dr Eleri Williams, Professor Andrew Cant, Dr Mario Abinun, Professor Sophie Hambleton, Professor Mary Slatter, Professor Andrew GenneryORCiD, Dr Stephen Owens
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025.Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is widely expressed and integral to inflammatory and cell death responses. Autosomal recessive RIPK1-deficiency, due to biallelic loss of function mutations in RIPK1, is a rare inborn error of immunity (IEI) resulting in uncontrolled necroptosis, apoptosis and inflammation. Although hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy, the extent to which disease may be driven by extra-hematopoietic effects of RIPK1-deficiency, which are non-amenable to HSCT, is not clear. We present a multi-centre, international review of an additional 5 RIPK1-deficient children who underwent HSCT. All patients presented with very early onset inflammatory bowel disease, 2 also suffered from inflammatory arthritis. Median age at transplant was 3 years (range 1—5 years); 1 received matched sibling marrow, 1 matched unrelated peripheral blood stem cells (PBSC), 2 TCRαβ/CD19-depleted PBSC from maternal-haploidentical donors, and 1 had TCRαβ/CD19-depleted PBSC from a mismatched unrelated donor. All received reduced-toxicity conditioning, based on treosulfan (n = 4) or busulfan (n = 1); 1 patient underwent a successful second transplant following autologous reconstitution. Four of five patients (80%) survived; 1 child died due to multi-drug resistant pseudomonas infection and multi-organ failure. With a median duration of 14 months follow-up, 2 survivors were disease-free, and 2 had substantially improving enteropathy. These findings demonstrated that HSCT is a potential curative therapy for RIPK1-deficiency.
Author(s): Walsh RB, McNaughton P, Nademi Z, Laberko A, Balashov D, Al-Mousa H, Arkwright PD, Wynn RF, Flood T, Williams E, Cant A, Abinun M, Hambleton S, Slatter M, Gennery AR, Lum SH, Owens S
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Immunology
Year: 2025
Volume: 45
Issue: 1
Online publication date: 06/01/2025
Acceptance date: 13/12/2024
Date deposited: 20/01/2025
ISSN (print): 0271-9142
ISSN (electronic): 1573-2592
Publisher: Springer
URL: https://doi.org/10.1007/s10875-024-01850-2
DOI: 10.1007/s10875-024-01850-2
Data Access Statement: No datasets were generated or analysed during the current study.
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