FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4306842010> ?p ?o ?g. }

• W4306842010 endingPage "272" @default.
• W4306842010 startingPage "258" @default.
• W4306842010 abstract "Significance Statement Lupus nephritis (LN) is the major cause of death among systemic lupus erythematosus patients, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes and finding potential therapeutic targets of LN is a major unmet clinical need. We identified a novel DDX58 pathogenic variant, R109C, that leads to RIG-I hyperactivation and type I IFN signaling upregulation by disrupting RIG-I autoinhibition, causing LN, which may respond to a JAK inhibitor. Genetic testing of families with multiple cases of LN that identifies this variant may lead to targeted therapy. Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes of LN can facilitate more individual treatment strategies. Methods We performed whole-exome sequencing in a cohort of Chinese patients with LN and identified variants of a disease-causing gene. Extensive biochemical, immunologic, and functional analyses assessed the effect of the variant on type I IFN signaling. We further investigated the effectiveness of targeted therapy using single-cell RNA sequencing. Results We identified a novel DDX58 pathogenic variant, R109C, in five unrelated families with LN. The DDX58 R109C variant is a gain-of-function mutation, elevating type I IFN signaling due to reduced autoinhibition, which leads to RIG-I hyperactivation, increased RIG-I K63 ubiquitination, and MAVS aggregation. Transcriptome analysis revealed an increased IFN signature in patient monocytes. Initiation of JAK inhibitor therapy (baricitinib 2 mg/d) effectively suppressed the IFN signal in one patient. Conclusions A novel DDX58 R109C variant that can cause LN connects IFNopathy and LN, suggesting targeted therapy on the basis of pathogenicity." @default.
• W4306842010 created "2022-10-20" @default.
• W4306842010 creator A5004509724 @default.
• W4306842010 creator A5007054845 @default.
• W4306842010 creator A5015704252 @default.
• W4306842010 creator A5019609939 @default.
• W4306842010 creator A5022261999 @default.
• W4306842010 creator A5026950221 @default.
• W4306842010 creator A5030911006 @default.
• W4306842010 creator A5032769690 @default.
• W4306842010 creator A5040629535 @default.
• W4306842010 creator A5041015608 @default.
• W4306842010 creator A5050534760 @default.
• W4306842010 creator A5050674552 @default.
• W4306842010 creator A5071375375 @default.
• W4306842010 creator A5071584579 @default.
• W4306842010 creator A5076768386 @default.
• W4306842010 creator A5081282224 @default.
• W4306842010 creator A5085002163 @default.
• W4306842010 date "2022-10-19" @default.
• W4306842010 modified "2023-10-16" @default.
• W4306842010 title "Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation" @default.
• W4306842010 cites W1791411745 @default.
• W4306842010 cites W1973610263 @default.
• W4306842010 cites W1986036781 @default.
• W4306842010 cites W1987469681 @default.
• W4306842010 cites W1987484835 @default.
• W4306842010 cites W1989032379 @default.
• W4306842010 cites W1993777863 @default.
• W4306842010 cites W2053476949 @default.
• W4306842010 cites W2061173833 @default.
• W4306842010 cites W2102260696 @default.
• W4306842010 cites W2106273198 @default.
• W4306842010 cites W2126385937 @default.
• W4306842010 cites W2141137217 @default.
• W4306842010 cites W2256482451 @default.
• W4306842010 cites W2337143478 @default.
• W4306842010 cites W2353041718 @default.
• W4306842010 cites W2562644378 @default.
• W4306842010 cites W2601896814 @default.
• W4306842010 cites W2782154111 @default.
• W4306842010 cites W2796690375 @default.
• W4306842010 cites W2810369524 @default.
• W4306842010 cites W2904017346 @default.
• W4306842010 cites W2906010089 @default.
• W4306842010 cites W2942369933 @default.
• W4306842010 cites W2995123617 @default.
• W4306842010 cites W3009051625 @default.
• W4306842010 cites W3026298997 @default.
• W4306842010 cites W3097229464 @default.
• W4306842010 cites W3107031282 @default.
• W4306842010 cites W3125073069 @default.
• W4306842010 cites W3154260878 @default.
• W4306842010 cites W3187580152 @default.
• W4306842010 cites W4221097082 @default.
• W4306842010 cites W4226166912 @default.
• W4306842010 doi "https://doi.org/10.1681/asn.2022040477" @default.
• W4306842010 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36261300" @default.
• W4306842010 hasPublicationYear "2022" @default.
• W4306842010 type Work @default.
• W4306842010 citedByCount "6" @default.
• W4306842010 countsByYear W43068420102023 @default.
• W4306842010 crossrefType "journal-article" @default.
• W4306842010 hasAuthorship W4306842010A5004509724 @default.
• W4306842010 hasAuthorship W4306842010A5007054845 @default.
• W4306842010 hasAuthorship W4306842010A5015704252 @default.
• W4306842010 hasAuthorship W4306842010A5019609939 @default.
• W4306842010 hasAuthorship W4306842010A5022261999 @default.
• W4306842010 hasAuthorship W4306842010A5026950221 @default.
• W4306842010 hasAuthorship W4306842010A5030911006 @default.
• W4306842010 hasAuthorship W4306842010A5032769690 @default.
• W4306842010 hasAuthorship W4306842010A5040629535 @default.
• W4306842010 hasAuthorship W4306842010A5041015608 @default.
• W4306842010 hasAuthorship W4306842010A5050534760 @default.
• W4306842010 hasAuthorship W4306842010A5050674552 @default.
• W4306842010 hasAuthorship W4306842010A5071375375 @default.
• W4306842010 hasAuthorship W4306842010A5071584579 @default.
• W4306842010 hasAuthorship W4306842010A5076768386 @default.
• W4306842010 hasAuthorship W4306842010A5081282224 @default.
• W4306842010 hasAuthorship W4306842010A5085002163 @default.
• W4306842010 hasConcept C104317684 @default.
• W4306842010 hasConcept C126322002 @default.
• W4306842010 hasConcept C127716648 @default.
• W4306842010 hasConcept C150194340 @default.
• W4306842010 hasConcept C162317418 @default.
• W4306842010 hasConcept C203014093 @default.
• W4306842010 hasConcept C2776912625 @default.
• W4306842010 hasConcept C2778366672 @default.
• W4306842010 hasConcept C2779134260 @default.
• W4306842010 hasConcept C2779912601 @default.
• W4306842010 hasConcept C501734568 @default.
• W4306842010 hasConcept C502942594 @default.
• W4306842010 hasConcept C54355233 @default.
• W4306842010 hasConcept C60644358 @default.
• W4306842010 hasConcept C71924100 @default.
• W4306842010 hasConcept C86803240 @default.
• W4306842010 hasConceptScore W4306842010C104317684 @default.
• W4306842010 hasConceptScore W4306842010C126322002 @default.

• next