Abstracts tagged "innate immunity"

Abstract Number: 1701 • ACR Convergence 2024
STING Pathway Activity in SLE Patient Serum Correlates with NFkB Activation, Autoantibody Levels, and a Unique Cytokine Profile That Drives Disease Activity
Hyun Hee Kim¹, Haochen Jiang², Tatiana Ort³, Gary Sims³ and Richard Hanna⁴, ¹AstraZeneca, Gaithersburg, MD, ²University of Nebraska, Omaha, NE, ³Immunology Biosciences, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, ⁴AstraZeneca, Dickerson, MD
Background/Purpose: Systemic lupus erythematosus (SLE) is a heterogenous systemic autoimmune disease which is associated with innate immune activation, type I IFN, inflammasome and NFkB-related cytokines.…
Abstract Number: 1712 • ACR Convergence 2024
Transcriptome Analysis Characterizes the Role of Monocytes in Ankylosing Spondylitis with TNF-blocker Treatment
Yulong Tang¹, Jiangnan Xie², Dachun Zhuo¹, Qi ZHU³, Jiucun Wang¹ and Jing Liu², ¹Fudan University, Shanghai, China (People's Republic), ²Fudan University, Shanghai, Shanghai, China (People's Republic), ³Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China (People's Republic)
Background/Purpose: Ankylosing spondylitis (AS) is an autoimmune and auto-inflammatory disease characterized by chronic inflammation of the spine, sacroiliac joint, and occasionally peripheral joints. TNF-α inhibitor…
Abstract Number: 1766 • ACR Convergence 2024
STAT2-Associated Type I Interferonopathy: A Masquerade of Infectious Susceptibility
Conor Gruber¹, Angelica Lee², Sofija Buta², Marta Martin Fernandez², Veronique Houdouin³, Jean-Laurent Casanova⁴, Alice Hadchouel⁵, Jacinta Bustamante⁵ and Dusan Bogunovic², ¹Mount Sinai Hospital, New York, NY, ²Columbia University, New York, NY, ³Robert Debré Hospital, Paris, France, ⁴Rockefeller University, New York, NY, ⁵Hôpital Necker-Enfants Malades, Paris, France
Background/Purpose: Type I IFN (IFN-I) signaling is a potent inflammatory pathway fundamental to antiviral immunity. In humans, loss of IFN-I activity underlies severe viral disease,…
Abstract Number: 1793 • ACR Convergence 2024
SLE Patient Serum and SLE-associated Danger Signals Impair Efferocytosis in Human Macrophages
Jessica Shannon and Rafael de Queiroz Prado, AstraZeneca, Gaithersburg, MD
Background/Purpose: Efficient clearance of apoptotic cells, known as efferocytosis, plays a pivotal role in maintaining self-tolerance. Dysfunction in efferocytosis is implicated in the pathogenesis of…
Abstract Number: 1796 • ACR Convergence 2024
Kidney Hematopoietic Stem and Progenitor Cells Contribute to Immune Cell Development and Pathology in Lupus Nephritis
Hansol Yi¹, Seyoung Jung², Mi-Ra Cho³, Yong-Gil Kim¹, Chang-Keun Lee¹, Bin Yoo¹, Jeongseok Lee² and Seokchan Hong¹, ¹Asan medical center, Seoul, Republic of Korea, ²Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea, ³Asan medical center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Background/Purpose: Hematopoiesis primarily occurs in the bone marrow (BM), where hematopoietic stem and progenitor cells (HSPCs) originate. However, non-lymphoid tissues outside the BM can contribute…
Abstract Number: 0040 • ACR Convergence 2024
Targeting Complement Factor B (CFB) via a Novel siRNA Therapy (AZD6912) to Treat Inflammatory Arthritis
Gary Sims¹, Mia Collins², Natalie Pursell³, Teneema Kuriakose¹, Fanyi Jiang⁴, Kristi Moore⁵, Lucie Bertrand⁵, Melissa Lasaro⁵, Jessica Neisen⁶, Scott Manetz⁷, Gabriel Wong⁸, Patrick Riley⁵, Iain McInnes⁹, Kyriakos Konstantinidis¹⁰ and David Close⁸, ¹Immunology Biosciences, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, ²Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, ³Dicerna, Lexington, ⁴Translation and Experimental Medicine, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, ⁵Alexion, AstraZeneca Rare Disease, New Haven, CT, ⁶Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, ⁷Clinical Pharmacology and Safety Science, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, ⁸Early Clinical Development, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, ⁹University of Glasgow, College of Medical Veterinary and Life Sciences, Glasgow, United Kingdom, ¹⁰Projects, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
Background/Purpose: New precision medicine guided therapies targeting alternate disease driving processes are required to improve clinical outcomes in RA. The complement pathway has long been…
Abstract Number: 1816 • ACR Convergence 2024
Paracrine WNT Signaling Drives Pro-fibrotic Metabolic Activation of Systemic Sclerosis Macrophages
Emily Morris¹, Helen Jarnagin², Heetaek Yang³, Alexandra Turnquist², Michael Whitfield⁴ and Patricia Pioli⁵, ¹Dartmouth College, Enfield, NH, ²Dartmouth College, Lebanon, NH, ³Dartmouth College, West Lebanon, NH, ⁴Geisel School of Medicine at Dartmouth, Hanover, NH, ⁵Geisel School of Medicine at Dartmouth, Lebanon, NH
Background/Purpose: While we have shown that systemic sclerosis (SSc) dermal fibroblasts and macrophages (MØs) engage in reciprocal activation mediated by exosomes via paracrine signaling, the…
Abstract Number: 0046 • ACR Convergence 2024
Impaired Neutrophil Extracellular Trap (NET) Degradation in Rheumatoid Arthritis (RA) and Pre-clinical RA Is Mediated by Anti-NET Antibodies
Jeba Atkia Maisha¹, Alina Sememenko², Jun Kim², Mario Navarrete², XIAOBO MENG¹, Hani El-Gabalawy¹ and Liam O'Neil¹, ¹University of Manitoba, Winnipeg, MB, Canada, ²University of Manitoba, Winnipeg, Canada
Background/Purpose: Rheumatoid Arthritis (RA) begins after a prolonged preclinical phase which is marked by the development of RA antibodies, typically against citrullinated proteins (ACPA). The…
Abstract Number: 1824 • ACR Convergence 2024
Skin Macrophage Subtypes and Impact of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis: Results from Single-cell Analyses of an Observational Data Set and a Phase I/II Randomized Controlled Trial
Juliette Ferrant¹, Alain Lescoat², Valérie Lecureur³, Marie Lelong³, John Varga⁴, Robert Lafyatis⁵, Johann Gudjonsson⁴ and Dinesh Khanna⁴, ¹CHU Rennes, Rennes, France, ²CHU Rennes - University Rennes 1, Rennes, France, ³Rennes University, Rennes, France, ⁴University of Michigan, Ann Arbor, MI, ⁵University of Pittsburgh, Pittsburgh, PA
Background/Purpose: Macrophages play a major role in dcSSc-related skin fibrosis, with a mixed M1-M2 activation profile relying on the activation of JAK/STAT. Tofacitinib, a pan-JAK…
Abstract Number: L02 • ACR Convergence 2023
Mutational Analysis of UNC93B1 Identifies Regulatory Regions Mutated in Human SLE
John Huizar¹, Victoria Rael², Julian Yano², Leianna Slayden³, Madeleine Weiss⁴, Robert Saxton⁴, Bo Liu⁵, Olivia Majer⁶ and Gregory Barton⁷, ¹UCSF, San Francisco, CA, ²Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, UC Berkeley, Berkeley, CA, ³HHMI at UC Berkeley, Berkeley, CA, ⁴UC Berkeley, Berkeley, CA, ⁵Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shangai, China, ⁶Max Planck Institute for Infection Biology, Berlin, Germany, ⁷UC Berkeley / HHMI, Berkeley, CA
Background/Purpose: Endosomal nucleic acid-sensing toll-like receptors 3, 7 and 9 are key innate immune sensors of dsRNA, ssRNA and ssDNA, respectively, whose activities must be…
Abstract Number: L08 • ACR Convergence 2023
Early Clinical Development of CIT-013, a First in Class NETosis Inhibitor, in a Randomized Phase I Dose Escalation Study in Healthy Volunteers Demonstrating Potent Inhibition of LPS Induced Neutrophil Extracellular Trap Formation
Leonie Middelink¹, Renato Chirivi², Helmuth van Es², Eric Meldrum², Peter van Zandvoort², Tirza Bruurmijn², Matthijs Moerland³ and Patrick Round², ¹Middelinc., Utrecht, Netherlands, ²Citryll BV, Oss, Netherlands, ³CHDR, Leiden, Netherlands
Background/Purpose: Aberrant Neutrophil Extracellular Traps (NETs) production contributes to the pathophysiology of multiple inflammatory and autoimmune diseases such as Rheumatoid arthritis (RA) Hidradenitis suppurativa (HS),…
Abstract Number: 0050 • ACR Convergence 2023
Anti-Citrullinated Histone Antibody CIT-013, a Dual Action Therapeutic for Neutrophil Extracellular Trap Associated Autoimmune Disease
Maarten van der Linden¹, Sangeeta Kumari¹, Daphne Montizaan¹, Stephanie van Dalen¹, Annemarie Kip¹, Martyn FOSTER², Inge Reinieren¹, Elsa Neubert³, Luise Erpenbeck⁴, Tirza Bruurmijn¹, Peter van Zandvoort¹, Paul Vink¹, Eric Meldrum⁵, Helmuth van Es¹ and Renato Chirivi¹, ¹Citryll BV, Oss, Netherlands, ²Experimental Pathology Consultancy, Benfleet, United Kingdom, ³Leiden Academic Centre for Drug Research, Leiden, Netherlands, ⁴University Medical Center Münster, General Dermatology and Venereology, Münster, Germany, ⁵Citryll BV, Basel, Switzerland
Background/Purpose: Neutrophil extracellular traps (NETs) contribute to the pathophysiology of multiple inflammatory and autoimmune diseases (Chirivi et al., 2021; DOI: 10.1038/s41423-020-0381-3). Targeting the NETosis pathway…
Abstract Number: 1498 • ACR Convergence 2023
First-in-Human Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of DS-7011a, an Anti-TLR7 Antagonistic Monoclonal Antibody for the Treatment of Systemic Lupus Erythematosus
Giorgio Senaldi¹, Aparna Mohan¹, Li Zhang¹, Jun Tanaka², Grishma Pandya³, Sindee Grossman³, Sarah Urbina⁴, Steven Reynolds⁵ and Alan Hand⁴, ¹Daiichi Sankyo, Basking Ridge, NJ, ²Daiichi Sankyo, Inc., Basking Ridge, NJ, ³Daiichi Sankyo Inc., Basking Ridge, NJ, ⁴Worldwide Clinical Trials, San Antonio, TX, ⁵Cenexel, Los Alamitos, CA
Background/Purpose: Toll-like receptor (TLR)7 is a pattern recognition receptor, whose ligands include nucleic acids and whose activation is part of the pathogenesis of systemic lupus…
Abstract Number: 0051 • ACR Convergence 2023
CD14+CD64+ Classical Monocytes Are the Main Producers of IL-23 at the Enthesis
Nicole McDermott¹, Thomas Macleod¹, Ala Altaie¹, Liz Straszynski², Robert Dunsmuir³, Vishal Borse³, Peter Loughenbury³, Davide Simone⁴, Stevephen Sansom⁴, Christopher Buckley⁴ and Dennis McGonagle⁵, ¹University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom, ²Leeds Institute of Medical Research at St. James’s, Leeds, United Kingdom, ³Leeds Teaching Hospital NHS Trust, Leeds, United Kingdom, ⁴Kennedy Institute of Rheumatology, Oxford, United Kingdom, ⁵Leeds Biomedical Research Centre, University of Leeds, Leeds, United Kingdom
Background/Purpose: IL-23 is a key cytokine involved in diseases such as psoriasis, psoriatic arthritis and spondyloarthropathies (SpA) and inflammatory bowel disease.IL-23 is produced by activated…
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…

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