ArticleThe Journal of experimental medicine2024
Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Assessment of the prevalence of neurological involvement in a pediatric cohort of children with lupus nephritis: retrospective multicenter study.Pediatric nephrology (Berlin, Germany) · 2026Article
- TLR7 in systemic lupus erythematosus: genetics and emerging therapies.Nature reviews. Rheumatology · 2026Review
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Monogenic autoimmune and autoinflammatory disorders in adulthood: recent discoveries and implications for rheumatology practice.Rheumatology (Oxford, England) · 2026Review
- Identification of a novel TLR7 gain-of-function variant that underlies systemic lupus erythematosus.Journal of human immunity · 2026Article
- Clinical characteristics, management, and hematopoietic cell transplantation of patients with TLR8 gain-of-function.Blood advances · 2026Article
- Novel TLR7 gain-of-function variant and review of the associated disease spectrum.Journal of human immunity · 2026Article
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Insights into the pathogenesis of childhood-onset SLE in the past decade.Nature reviews. Rheumatology · 2026Review
- TLR7 signaling aggravates lung inflammation associated with increased anti-Scl-70 autoantibody production in murine bleomycin-induced systemic sclerosis.Frontiers in immunology · 2026Article
- Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.Current rheumatology reports · 2025Review
- Cutaneous lupus erythematosus - from pathogenesis to targeted therapy.Nature reviews. Rheumatology · 2025Review
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- Single-centre comparison of non-familial, familial and monogenic lupus.Rheumatology (Oxford, England) · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Interferons in health and disease.Cell · 2025Review
- Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease.Nature reviews. Genetics · 2025Review
- Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains.The Journal of experimental medicine · 2025Article
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32 authors.
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Abstract
UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.
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