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Lookup NU author(s): Dr Stephen Owens
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026. The sarcoma (Src) family of non-receptor tyrosine kinases (SFKs) regulate innate immunity through their roles in signal transduction and cell migration, adhesion and proliferation. Germline pathogenic variants in this key kinase group are rare but increasingly recognised as causes of autoinflammatory disease. We identified three unrelated kindreds with SFK-associated vasculitis. In Family A, we report a child with systemic vasculitis due to a nonsense heterozygous variant in HCK (p.Y515X) who was subsequently treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT), the first use of this approach in SFK-related disease. In Family B, we identified a novel HCK missense variant (p.Y522F) causing a cutaneous-limited phenotype. In Family C, we describe a large pedigree carrying a novel missense variant in FGR (p.Y523H), establishing FGR as a new cause of monogenic vasculitis. In all families, disease-onset was neonatal with vasculitic rash, variably progressing to systemic involvement including lung disease. Functional studies demonstrated reduced Hck and Fgr protein expression and enhanced p-STAT1 and p-STAT5 signalling in monocytes and lymphocytes. With striking similarities in the clinical phenotypes and underlying molecular mechanisms, these cases expand the spectrum of sarcoma (Src) family of non-receptor tyrosine kinase-associated autoinflammatory disease, and support this as a distinct group that we propose is termed the “autoinflammatory Src-opathies (sarcopathies)”.
Author(s): Price-Kuehne F, Burleigh A, Hong Y, Omoyinmi E, Petrof G, Malik G, McLellan K, Owens S, Lum SH, Dawson P, Turtsevich I, Robertson J, Stolagiewicz N, Roberts G, Eleftheriou D, Brogan P
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Immunology
Year: 2026
Volume: 46
Online publication date: 01/04/2026
Acceptance date: 08/02/2026
Date deposited: 26/05/2026
ISSN (print): 0271-9142
ISSN (electronic): 1573-2592
Publisher: Springer Nature
URL: https://doi.org/10.1007/s10875-026-01998-z
DOI: 10.1007/s10875-026-01998-z
Data Access Statement: The novel HCK and FGR pathogenic variants are submitted to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar) and the Infevers database (https://infevers.umai-montpellier.fr/web). Further data is available upon reasonable request to the corresponding author.
PubMed id: 41920357
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