Abstract Number: 0733 • ACR Convergence 2023
Global Identification of Lupus Genetic Risk Variants Facilitating the Type I Interferon Pathway Through CRISPR-based Genomic Screening
Background/Purpose: Genome-Wide Association Studies (GWAS) have unveiled over 1000 risk variants for lupus, predominantly situated in non-coding genomic regions. Their functional roles, especially their potential…Abstract Number: 1586 • ACR Convergence 2023
Keratinocyte VISTA Suppresses Skin IFN-I Production by Regulating DNA Damage Repair and Cytosolic DNA Sensing
Background/Purpose: Persistent production of type I interferons (IFN-Is) is one of the hallmarks of lupus skin disease that is exacerbated by ultraviolet (UV) light. We…Abstract Number: 0762 • ACR Convergence 2023
Liver Disease Is a Common Feature of HA20 That Causes Significant Morbidity Associated with Interferon Induction
Background/Purpose: Heterozygous loss-of-function TNFAIP3 mutations cause A20 haploinsufficiency (HA20), an early-onset immune dysregulatory disease1. While HA20 was initially described as an inherited form of Behcet’s…Abstract Number: 1587 • ACR Convergence 2023
Mitochondrial Z-DNA and ZBP1 Drive Autoimmune Photosensitivity
Background/Purpose: Autoimmune photosensitivity is observed in type I Interferon (IFN) mediated diseases such as systemic and cutaneous lupus erythematosus (SLE/CLE) and dermatomyositis. Type I IFN…Abstract Number: 0788 • ACR Convergence 2023
Whole Exome Sequencing and Evolutionary Action Missense Mutation Analysis Identifies MICB as a New SSc Susceptibility Locus and the Interferon Pathway as Contributors to SSc Pathogenesis
Background/Purpose: Systemic Sclerosis (SSc) is characterized by fibrosis of the skin and internal organs associated with vasculopathy and autoantibodies and exhibiting wide clinical heterogeneity. Contributors…Abstract Number: 1590 • ACR Convergence 2023
Autoimmune Pathway Blockade by a Potent Orally Bioavailable STING Antagonist
Background/Purpose: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a key innate immune mediator of autoimmune and inflammatory diseases. However,…Abstract Number: 0792 • ACR Convergence 2023
Single Cell RNA-seq of Myeloid Cells from Systemic Sclerosis Patients Identifies Circulating Monocyte Population with Interferon Signature Associated with Interstitial Lung Disease
Background/Purpose: Growing evidence supports a critical role for innate immunity in systemic sclerosis (SSc) pathogenesis. Altered myeloid cell numbers and functions have been implicated in…Abstract Number: 1658 • ACR Convergence 2023
Title: Inflammatory Arthritis Across the Age-Spectrum: Single-Cell Profiling of the Inflamed Synovium in Children with Juvenile Idiopathic Arthritis
Background/Purpose: Understanding the unique and shared pathogenic processes between childhood-onset and adult-onset inflammatory arthritides is needed to guide more effective drug development and their application…Abstract Number: 0010 • ACR Convergence 2023
A Potential Mechanism for Major Adverse Cardiac Events Associated with JAK Inhibitors: JAK Inhibitor Withdrawal Causes Urokinase Release by Primed STAT Signaling
Background/Purpose: Sjögren’s Disease (SjD) has high glandular IFNg levels, associated with disease activity and lymphoma risk. We showed that IFNg-stimulated minor salivary gland (SG)-mesenchymal stromal…Abstract Number: 0886 • ACR Convergence 2023
Neonatal Roseolovirus Infection Predisposes to Development of Lupus-like Disease After TLR7 Stimulation
Background/Purpose: Viral infections have been implicated as major factors in autoimmune disease but demonstrating causality is often challenging. We found that neonatal infection with a…Abstract Number: 1660 • ACR Convergence 2023
Still’s Disease Patients with High Interferon-stimulated Gene Expression Have Enrichment of Rare, de Novo and Recessive Protein Altering Variants in Innate Immune Pathways
Background/Purpose: Still’s disease (systemic juvenile idiopathic arthritis in children, adult-onset Still’s disease in adults) is an enigmatic inflammatory condition that affects people of all ages.…Abstract Number: 0055 • ACR Convergence 2023
Elevated LINE-1 Expression in SLE Keratinocytes Leads to LINE-1 Reverse Transcriptase-dependent Type I Interferon Responses
Background/Purpose: Long Interspersed Element-1 (LINE-1) are retrotransposable DNA elements that make up ~17% of the human genome, and their role in health and disease is…Abstract Number: 0891 • ACR Convergence 2023
Selective and Potent Inhibition of Cyclic GMP-AMP Synthase (cGAS) Fully Normalizes Autoinflammation Across Tissues in a Trex1-/- Mouse Model for Type I Interferonopathies
Background/Purpose: The cGAS enzyme is a sensor of cytosolic double-strand (ds) DNA. It serves to detect viruses and elicits an acute, transient cGAMP-STING mediated type…Abstract Number: 1664 • ACR Convergence 2023
Fibroblast Specific Interferon Regulatory Factor 7 (IRF7) Expression Is a Key Link Between Type I Interferon Activation and the Exaggerated Dermal and Pulmonary Fibrosis in Systemic Sclerosis
Background/Purpose: A prominent interferon (IFN) activation signature has been observed at the peripheral blood and end-organ levels in systemic sclerosis (SSc). However, the mechanisms by…Abstract Number: 0056 • ACR Convergence 2023
The Activation of cGAS-STING Pathway in Systemic Lupus Erythematosus
Background/Purpose: The majority of patients with SLE show a striking Type I Interferon (IFN-I) signature in their peripheral blood. Although this signature can be generated…
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