Abstracts tagged "interferon"

Abstract Number: 0733 • ACR Convergence 2023
Global Identification of Lupus Genetic Risk Variants Facilitating the Type I Interferon Pathway Through CRISPR-based Genomic Screening
Guojun Hou¹, Xinyi Zhu¹, Yutong Zhang¹, Zhaorui Cheng¹ and Nan Shen², ¹Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University (SJTUSM), Shanghai, China, ²Shanghai Jiao Tong University School of Medicine, Shanghai, China
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
Zachary Peters¹, Lindsay Mendyka², Sicong Shan¹, William Rigby³, Christopher Burns⁴, Randolph Noelle⁵ and Sladjana Skopelja-Gardner⁴, ¹Dartmouth College, Hanover, NH, ²Dartmouth Hitchcock, Lebanon, NH, ³Dartmouth-Hitchcock, Norwich, VT, ⁴Dartmouth Hitchcock Medical Center, Lebanon, NH, ⁵Geisel School of Medicine at Dartmouth, Hanover, NH
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
Magdalena Harasimowicz¹, Deborah Stone², Manuel Carpio Tumba¹, Tina Romeo², Urekha Karri¹, Patrycja Hoffmann³, Helen Leavis⁴, Alexander Miethke⁵, Theo Heller², Anjali Rai², Ivona Aksentijevich², amanda ombrello⁶, Daniel Kastner⁷ and Daniella Schwartz¹, ¹University of Pittsburgh, Pittsburgh, PA, ²NIH, Bethesda, MD, ³NIH, Vienna, VA, ⁴Infection Immunity Utrecht, Utrecht, Netherlands, ⁵Cincinnati Children's Hospital, Cincinnati, OH, ⁶National Institutes of Health, Rockville, MD, ⁷National Human Genome Research Institute, Bethesda, MD
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
Benjamin Klein, Mack Reynolds, Bin Xu, Mehrnaz Gharaee-Kermani, Amanda Victory, Shannon Loftus, Mary O'Riordan and J. Michelle Kahlenberg, University of Michigan, Ann Arbor, MI
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
Shamika Ketkar¹, Hongzheng Dai¹, Brian Dawson¹, Lindsay Burrage¹, David Murdock¹, Jennifer Asmussen¹, Kevin Wilhelm¹, Olivier Lichtarge¹, Martin Kerick², Javier Martin³, Shervin Assassi⁴, Brendan Lee¹ and Maureen Mayes⁵, ¹Baylor College of Medicine, Houston, TX, ²Spanish National Research Council, Granada, Spain, ³Instituto de Parasitologia y Biomedicina Lopez-Neyra - CSIC, Granada, Spain, ⁴University of Texas McGovern Medical School at Houston, Houston, TX, ⁵Division of Rheumatology, University of Texas McGovern Medical School, Houston, TX
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
Min Yang¹, Hailong Li¹, yangyang liu¹, lili yao¹, Jing Lin¹, Zhi xie² and Wenge zhong¹, ¹Regor Therapeutics, Shanghai, China, ²Regor Pharmaceuticals, Inc., San Francisco, CA
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
Richard Ainsworth¹, Kim Taylor², Ye Cao³, Takanori Sasaki⁴, Deepak Rao⁵, Nunzio Bottini⁶ and Francesco Boin¹, ¹Cedars-Sinai Medical Center, Los Angeles, CA, ²University of California San Francisco, San Francisco, CA, ³Brigham and Women's Hospital, Boston, MA, ⁴Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ⁵Brigham and Women's Hospital, Boston, MA, ⁶University of California, San Francisco, CA
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
Chrissy Bolton¹, Christopher Mahony², Charlotte Smith², Vicky Alexiou³, Huong Nguyen³, Patricia Reis-Nisa², Søren Lomholt⁴, Annie Hackland², Sugrah Sultan⁵, Klaudia Kupiec³, Sunit Davda⁶, Charlene Foley⁶, Calliope Dendrou¹, Elizabeth C Rosser⁷, Accelerating Medicines Partnership Program RA SLE Network⁸, Anna Helena Jonsson⁹, Fan Zhang¹⁰, Michael Brenner¹¹, Soumya Raychaudhuri⁹, Christopher Buckley¹, Manigandan Thyagarajan⁵, Zishan Shiekh⁵, Sandrine Compeyrot-Lacassagne⁶, Samantha Chippington⁶, Mark Coles¹, Eslam Al-Abadi⁵, Andrew Filer², Tissue Research in Childhood Onset Inflammatory Arthritis (TRICIA) Consortium¹², Lucy R Wedderburn³ and Adam Croft², ¹University of Oxford, Oxford, United Kingdom, ²University of Birmingham, Birmingham, United Kingdom, ³UCL Great Ormond Street Institute of Child Health, London, United Kingdom, ⁴Aarhus University, Aarhus, Denmark, ⁵Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom, ⁶Great Ormond Street Hospital, London, United Kingdom, ⁷University College London, London, United Kingdom, ⁸Cedars-Sinai Medical Center, Los Angeles, CA, ⁹Brigham and Women's Hospital, Boston, MA, ¹⁰University of Colorado, Aurora, CO, ¹¹Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ¹²MRC, Birmingham, United Kingdom
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
Sara McCoy¹, Ilya Gurevic² and jacques Galipeau², ¹University of Wisconsin School of Medicine and Public Health, Middleton, WI, ²University of Wisconsin, Madison, WI
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
Tarin Bigley¹, Eden Xue¹, Lifei Zhu¹, Li-ping Yang¹ and wayne Yokoyama², ¹Washington University in St. Louis, St. Louis, MO, ²Washington University School of Medicine, St. Louis, MO
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
Mariana Correia Marques¹, Zuoming Deng², Navid Chowdhury², Elizabeth Schmitz³, Alana Platukus⁴, Stephen Brooks⁵, Carol Lake², Ly-Lan Bergeron², Michelle Millwood² and Michael Ombrello⁶, ¹National Institute of Arthritis & Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, ²National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, ³National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), St. Louis, MO, ⁴National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Philadelphia, PA, ⁵Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skins Diseases, National Institutes of Health, Bethesda, MD, ⁶National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), North Bethesda, MD
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
Wenyan Miao¹, Daniel Rios¹, Mehrnaz Gharaee-Kermani², Craig Dobry², Artur Jaroszewicz¹, Cedric Arisdakessian¹, Enrique Garcia-Rivera¹, Nafeeza Hafeez¹, Brian Desrosiers¹, Jess Floro¹, Jared Steranka¹, Menachem Fromer¹, Dennis Zaller¹ and J. Michelle Kahlenberg², ¹Rome Therapeutics, Boston, MA, ²University of Michigan, Ann Arbor, MI
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
Arnaud Bourin¹, Zuzana Hořejší², Isabelle Cambré¹, Juraj Dobiaš², Mikhail Klychnikov², Radek Liboska², Maroš Smolíček², Zdeněk Vavřina², Wanda Haeck¹, Hugo Klaassen¹, Marnik Nijs¹, Kristine Metzger¹, Sandro Boland¹, Dries De Clercq¹, Sara Allasia¹, Gunter Carlens¹, Patrick Chaltin³, Arnaud Marchand¹, Ondřej Páv², Matthias Versele¹ and Gabriel Birkuš², ¹Centre for Drug Design and Discovery (CD3) - Cistim, Leuven, Belgium, ²Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic, ³Centre for Drug Design and Discovery (CD3) - KU Leuven, Leuven, Belgium
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
Minghua Wu¹, Jerry Alonso², Julio charles², Brian Skaug², Tingting Mills³, Maureen Mayes² and Shervin Assassi⁴, ¹Department of Internal Medicine, Division of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX, ²Division of Rheumatology, University of Texas McGovern Medical School, Houston, TX, ³Biochemistry Department, University of Texas McGovern Medical School, Houston, TX, ⁴University of Texas McGovern Medical School at Houston, Houston, TX
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
Jie An¹, Stephen Wilson², Jill Henault³ and Keith Elkon¹, ¹University of Washington, Seattle, WA, ²Bristol Myers Squibb, Cambridge, MA, ³Bristol Myers Squibb, Acton, MA
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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