Clinical and immunological characterization of a child with a homozygous TBK1 kinase-domain truncation.

Authors

Busra Seniz Demir, Sumeyra Ozdemir Cicek, Mohammad Ahmad Houran, Zehra Busra Azizoglu, Mine Asan, Hasan Bas, Benhur Sirvan Cetin, Hakan Gumus, Serife Erdem, Halit Canatan, Ekrem Unal, Elena Wy Hsieh, Aysenur Pac Kısaarslan, Ahmet Eken

Published in

Immunologic research. Volume 74. Issue 1. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

TBK1 is a serine-tyrosine kinase protein that transmits signals from pattern recognition receptors to the NF-κB pathway leading to production of Type 1 Interferons. Mutations in this protein have been associated with arthritis, vasculitis, herpes simplex encephalitis and amyotrophic lateral sclerosis. In the current study, we characterized the functional consequences of a TBK1-variant bearing a truncation in exon 4 and 5 in a patient with poly arthritis resembling juvenile idiopathic arthritis and necrotizing encephalitis. The truncation was associated with reduced TBK1 protein abundance and altered phosphorylation. The variant was associated with increased basal/and or Poly-I: C induced IL-6, TNFα, IL-1β and IL-18 and type 1 Interferon ex vivo. Our findings expand the phenotypic spectrum of TBK1 loss-of-function variants and may provide insight into the management of immune dysregulation in affected patients.

PMID:
42704422
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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