Recurrent severe viral infection in a child with inherited complete TBK1 deficiency
TANK-binding kinase 1 (TBK1) acts at the crossroads of various host immune pathways. Autosomal dominant (AD) and recessive (AR) TBK1 deficiencies have been reported in human patients with herpes simplex encephalitis and SARS-CoV-2 pneumonia (AD deficiency) or systemic inflammation (AR deficiency). We describe here a Turkish boy, born to consanguineous parents and homozygous for a loss-of-function mutation of <i>TBK1</i>, who had experienced recurrent vesicular skin eruptions presumably triggered by herpesviral infection and five episodes of viral pneumonia since the age of 2 mo. Whole-exome sequencing identified a biallelic mutation of the <i>TBK1</i> gene (<i>NM_013254.4</i>: c.922C>T, p.Arg308Ter). The induction of <i>IFNB</i>, <i>IFNL1</i>, <i>IFIT1</i>, and <i>IL6</i> was abolished or severely impaired in SV40-fibroblasts from the patient following stimulation of the TLR3 or RIG-I/MDA5-RIG-I pathways. The patient underwent stem-cell transplantation, but unfortunately succumbed to suspected post-viral acute disseminated encephalomyelitis at the age of 2.5 years. AD or AR TBK1 deficiency should be considered in patients with severe viral infections.
Authors
- Yasin Karalı (ORCID: https://orcid.org/0000-0002-1245-4232)
- Michael R. Wilson (ORCID: https://orcid.org/0000-0002-8705-5084)
- Aaron Bodansky (ORCID: https://orcid.org/0000-0001-8943-8233)
- Jean‐Laurent Casanova (ORCID: https://orcid.org/0000-0002-7782-4169)
- Koray Yalçın (ORCID: https://orcid.org/0000-0003-3454-9870)
- Shuxiang Zhao (ORCID: https://orcid.org/0000-0001-9185-6813)
- Sara Şebnem Kılıç (ORCID: https://orcid.org/0000-0001-8571-2581)
- Shen‐Ying Zhang (ORCID: https://orcid.org/0000-0002-9449-3672)
- Zhiyong Liu (ORCID: https://orcid.org/0000-0001-6473-348X)
- Debanjana Chakravarty (ORCID: https://orcid.org/0000-0002-4607-9143)
Institutions
- Bahçeşehir University (TR)
- Bursa Uludağ Üni̇versi̇tesi̇ (TR)
- Howard Hughes Medical Institute (US)
- Inserm (FR)
- University of California, San Francisco (US)
- Université Paris Cité (FR)
- Institut Necker Enfants Malades (FR)
- Hospital for Sick Children Pediatric Center (US)
- Institut des Maladies Génétiques Imagine (FR)
- Rockefeller University (US)
Publication Details
- Journal
- Journal of Human Immunity
- Published
- 2025-11-14
- DOI
- https://doi.org/10.70962/jhi.20250058
- Citations
- 1
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- St. Giles Foundation
- Fondation du Souffle
- Institut des maladies génétiques Imagine
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- National Institutes of Health
- National Center for Advancing Translational Sciences