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Systemic Lupus Erythematosus due to Gain-of-Function Mutation in UNC93B1

Year: 2022
Type: preprint
Study design: Case Report
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the loss of tolerance to nuclear antigens. Activation of type I interferon (IFN) induced by immune recognition of self-nucleic acids by endosomal Toll-like receptors (TLR) is central to SLE pathogenesis. In two siblings with early-onset SLE, we identified a homozygous mutation in UNC93B1, encoding a multi-transmembrane protein required for trafficking and maturation of endosomal nucleic acid-sensing TLRs. The mutation alters the interaction of UNC93B1 with TLR7 leading to TLR7 hyperactivation with constitutive type I IFN signaling. Moreover, we demonstrate that treatment with the Janus kinase inhibitor ruxolitinib is of therapeutic value.
DOI: 10.21203/rs.3.rs-1877908/v1
Authors: Christine Wolf, Barbara Kind, Ee Lyn Lim, Gregor Dückers, Sarah Koss, Kerstin Engel, Eusebia Lara-Villacanas, Kathrin Siepermann, Tim Niehues, Carina C. de Oliveira Mann, Eicke Latz, Olivia Majer, Min Ae Lee-Kirsch
Institutions: Technische Universität Dresden, Max Planck Institute for Infection Biology, Helios Klinikum Krefeld, Klinikum Dortmund, Technical University of Munich, University of Bonn
Language: English
Subfield: Rheumatology
Field: Medicine
Open Access status: green
Awards: SFB 1454: Metaflammation und Zelluläre Programmierung, TRR 237: NukleinsäureImmunität, G309027104, G3864451752, Zyklische Nukleotide als Sekundäre Botenstoffe in Antiviraler Immunität und Entwicklungsbiologie, SFB 1403: Zelltod in Immunität, Entzündungen und Erkrankungen, G727481207, KFO 249: Defekte des angeborenen Immunsystems bei autoinflammatorischen und autoimmunologischen Erkrankungen
OpenAlex ID: W4286203167
Cites: 17
Cited by: 1
Related to: 10