Abstracts tagged "innate immunity"

Abstract Number: 0947 • ACR Convergence 2023
Fcγ Receptors Define Pro-Phagocytic Macrophages and Trigger Pro-Inflammatory Responses in Patients with Systemic Sclerosis
Amela Hukara¹, Gino Andrea Bonazza¹, Tracy Tabib², Raphael Micheroli¹, Suzana Jordan³, Kristina Bürki¹, Sylvie Schlitz Schönbächler¹, Adrian Ciurea⁴, Oliver Distler³, Robert Lafyatis⁵, Przemyslaw Blyszczuk¹ and Gabriela Kania¹, ¹Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, ²Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, ³Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, ⁴University Hospital Zurich, Zürich, Switzerland, ⁵University of Pittsburgh, Pittsburgh, PA
Background/Purpose: Fcy receptors (FcγR) are opsonic phagocytic receptors, requiring tight regulations to prevent uncontrolled activation of pro-inflammatory phagocytosis. SSc macrophages display an alternatively-activated profibrotic phenotype.…
Abstract Number: 0049 • ACR Convergence 2023
Soluble Uric Acid Is an Endogenous Inhibitor of CD38
Shijie Wen¹, Hiroshi Arakawa¹, Shigeru Yokoyama², Yoshiyuki Shirasaka¹, Haruhiro Higashida³ and Ikumi Tamai¹, ¹Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan, ²Research Center for Child Mental Development, Kanazawa University; Division of Socio-Cognitive-Neuroscience, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Kanazawa University, Kanazawa, Japan, ³Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan
Background/Purpose: CD38 is the main NAD+-degrading enzyme that plays a key role in innate immunity, aging, cancer, and metabolic disorders. Pharmacological inhibition of CD38 has…
Abstract Number: 1329 • ACR Convergence 2023
R851, a Potent Second Generation IRAK1 and IRAK4 Inhibitor Suppresses IL-6 in Vitro and in Vivo for the Treatment of Rheumatoid Arthritis
Yan Chen¹, Sothy Yi¹, Vadim Markovtsov¹, Bhushan Samant¹, Andrew Chow¹, Esteban Masuda¹ and Simon Shaw², ¹Rigel Pharmaceuticals, Inc, South San Francisco, CA, ²Rigel Pharmaceuticals, Inc., South San Francisco, CA
Background/Purpose: The Toll-Like Receptor family (except TLR3) signal through IRAK4 and IRAK1 to produce an array of cytokines (including IL-6, IL-23 and TNFα in response…
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…
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…
Abstract Number: 1662 • ACR Convergence 2023
Chronic Excess IL-18 Induces NK Deficiency, but Drives Hyperinflammation via CD8 T-cell Cytokine Overproduction and Selective Immunodeficiency
Jemy Varghese¹, Scott Canna¹, Emily Landy², Laurence Eisenlohr¹, Elise Peauroi³, Vinh Dang¹, Anastasia Frank-Kamenetskii⁴ and Jeremy Morrissette⁵, ¹Children's Hospital of Philadelphia, Philadelphia, PA, ²University of Pittsburgh, Pittsburgh, PA, ³University of Pennsylvania, Philadelphia, PA, ⁴CHOP/UPENN, Philadelphia, PA, ⁵University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA
Background/Purpose: Systemic Juvenile Idiopathic Arthritis (SJIA) and Macrophage Activation Syndrome (MAS) are associated with highly elevated peripheral blood levels of the inflammasome-activated cytokine IL-18 and…
Abstract Number: 0259 • ACR Convergence 2023
Preliminary Experience with a Novel “Fix” for Deep Epitope and Transcriptional Phenotyping of Fragile Cells from Autoinflammatory Flares
Hallie Carol¹, Emily Landy² and Scott Canna¹, ¹Children's Hospital of Philadelphia, Philadelphia, PA, ²University of Pittsburgh, Pittsburgh, PA
Background/Purpose: Autoinflammatory diseases (AID) are characterized by inflammation and immunopathology due to primary defects in the innate immune response. Neutrophils (PMN) feature prominently in the…
Abstract Number: 1676 • ACR Convergence 2023
Tofacitinib Accelerates in Vitro Clot Formation and Delays Clot Lysis in Rheumatoid Arthritis Blood by Enhancement of Macrophage TLR4 Mediated Cytokine Responses- a New Angle on Thrombosis with JAKi in Rheumatology
Paula David¹, Thomas Macleod², Yu Shi³, Payal Ganguly¹, Cedric Duval³, Mark Harland¹, Chi Wong¹, Benazir Saleem⁴ and Dennis McGonagle⁵, ¹University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Leeds, United Kingdom, ²University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom, ³Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom, ⁴Leeds Teaching Hospitals NHS Trust, Rheumatology, Chapel Allerton Hospital, Leeds, United Kingdom, ⁵Leeds Biomedical Research Centre, University of Leeds, Leeds, United Kingdom
Background/Purpose: Rheumatoid Arthritis (RA) patients treated with Janus Kinase inhibitors (JAKi) have reportedly higher venous thromboembolism (VTE) risk and atherosclerotic-related complications including myocardial infarction (1).Although…
Abstract Number: 0757 • ACR Convergence 2023
Identification of 23 Novel COPA Rare Exonic Non-Synonymous Variants and Their Associated Autoimmune and Inflammatory Clinical Phenotypes Among 53,364 Individuals
Pierre-Antoine Juge¹, Gregory McDermott², Keigo Hayashi², Jing Cui³, Clémence David-Gabarre⁴, Marie-Louis Frémond⁴, Holly Wobma⁵, Soumya Raychaudhuri², Elizabeth Karlson², Philippe Dieudé⁶ and Jeffrey Sparks⁷, ¹Division of Rheumatology, Inflammation, and Immunity Brigham & Women's Hospital, Boston, MA, ²Brigham and Women's Hospital, Boston, MA, ³Brigham and Women's Hospital, Boston, MA, ⁴Imagine, Paris, France, ⁵Division of Immunology, Boston Children's Hospital, Boston, MA, ⁶Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, INSERM UMR1152, University de Paris Cité, Department of Rheumatology, Paris, France, ⁷Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Background/Purpose: COPA syndrome is a rare, severe monogenic autoinflammatory/autoimmune disorder with variable penetrance, most commonly affecting the lungs and joints. It is caused by dominant…
Abstract Number: 1712 • ACR Convergence 2023
Identification and Functional Characterization of Eight CANDLE/PRAAS Causing Proteasome Variants in Five Unrelated Patients
Adriana Almeida de Jesus¹, Jonas J. Papendorf², Frederic Ebstein³, Sara Alehashemi⁴, Daniela Pioto⁵, Anna Kozlova⁶, Maria Teresa TErreri⁷, Anna Shcherbina⁶, Andre Rastegar⁸, Marta Rodrigues⁹, Renan Pereira¹⁰, Sophia Park¹¹, Bin Lin¹², Kat Uss¹¹, Ana Flavia da Silva Pina⁵, FLAVIO SZTAJNBOK¹³, Sofia Torreggiani¹⁴, Jennifer Stoddard¹⁵, Julie Niemela¹⁵, Sergio Rosenzweig¹⁵, Adriana Fonseca¹⁶, Marietta De Guzman¹⁷, Nicole Micheloni⁵, Melissa Fraga⁵, Sandro Perazzio¹⁸, Raphaela Goldbach-Mansky¹⁹ and Elke Krueger², ¹NIAID, NIH, Bethesda, MD, ²Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany, ³Nantes Université, Nantes, France, ⁴NIH/NIAID/TADS, Clarksville, MD, ⁵Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil, ⁶Center for Pediatric Hematology, Oncology, Immunology, Moscow, Russia, ⁷UNIFESP, São Paulo, Brazil, ⁸NIH, Bethesda, MD, ⁹Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil, ¹⁰Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, ¹¹Translational Autoinflammatory Diseases Section, LCIM, NIAID, NIH, Bethesda, MD, ¹²Translational Autoinflammatory Diseases Section l LCIM, NIAID, NIH, Bethesda, MD, ¹³UFRJ/UERJ, São Paulo, Brazil, ¹⁴University of Maryland Baltimore, Baltimore, MD, ¹⁵Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, MD, ¹⁶Instituto de Puericultura e Pediatria Martagao Gesteira / Universidade Federal do Rio de Janeiro, Rio De Janeiro, Brazil, ¹⁷Baylor College of Medicine, Houston, TX, ¹⁸Universidade de Sao Paulo (Unifesp); Universidade de São Paulo (USP); Fleury Laboratories, São Paulo, Brazil, ¹⁹NIH/NIAID, Potomac, MD
Background/Purpose: Mutations in genes coding for 20S proteasome subunits or proteasome assembly helpers cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or…
Abstract Number: 0796 • ACR Convergence 2023
Role of Group 2 Innate Lymphoid Cells in the Pathogenesis of Rheumatoid Arthritis
Anders Nguyen¹, Agnieszka Lastowska¹, Miriam Bollmann¹, Symeon Kourmoulakis¹, Charlotte E. van der Plas¹, Anna-Karin Hultgård Ekwall², Dietmar M. Zaiss³, Gary S Firestein⁴ and Mattias N.D Svensson⁵, ¹Department of Rheumatology and Inflammation research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, ²Department of Rheumatology and Inflammation research, Sahlgrenska Academy, University of Gothenburg, Kullavik, Sweden, ³Faculty of Medicine, Department of Immune Medicine, University of Regensburg, Regensburg, Germany, Regensburg, Germany, ⁴Department of Medicine, University of California San Diego, La Jolla, CA, ⁵University of Gothenburg, Gothenburg, Sweden
Background/Purpose: Immune-cell mediated activation of joint-lining fibroblast-like synoviocytes (FLS) play a key role in joint inflammation and destruction during Rheumatoid arthritis (RA). Thus, identifying factors…
Abstract Number: 1761 • ACR Convergence 2023
JAK/STAT Inhibition Modifies the Innate Lymphoid Cells 1 Immune Response in Patients with Rheumatoid Arthritis
Lidia La Barbera¹, Marianna Lo Pizzo¹, Chiara Rizzo¹, Leila Mohammadnezhad¹, federica Camarda¹, Francesco Ciccia² and Giuliana Guggino¹, ¹University of Palermo, Palermo, Italy, ²University of Campania - Luigi Vanvitelli, Naples, Italy
Background/Purpose: Recent evidence suggests that innate lymphoid cells (ILCs) might be involved in rheumatoid arthritis (RA) pathogenesis and individuals at risk of RA exhibited an…

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