Abstracts tagged "innate immunity"

Abstract Number: L01 • ACR Convergence 2024
Targeted Exosite Inhibition of STING Activation of TBK1 Selectively Blocks Type I Interferon and NFκB Responses for Treatment of Autoimmune Diseases
Matthew Martin¹, Erik Wilker¹, Diana Gikunju¹, Usha Narayanan¹, Unnati Pandya¹, Vijetha Prakash¹, Ashley Edwards¹, Sameer Kawatkar¹, Tenghui Chen¹, Ragunath Chandran¹, Sai Sunder¹, Sumathi Biradar¹, Joerg Distler², Alexandra Joseph¹, Stephanos Ioannidis¹ and Bhavatarini Vangamudi¹, ¹Exo Therapeutics, Cambridge, MA, ²Exo Therapeutics, Düsseldorf, Germany
Background/Purpose: The cGAS-TBK1-STING pathway senses nucleic acids for innate immunity. Aberrant activation of the pathway is linked to autoimmune diseases including Systemic and Cutaneous Lupus…
Abstract Number: 0967 • ACR Convergence 2024
Transcriptional Heterogeneity of Immune Cells in the Esophagus of Systemic Sclerosis Patients: A Comparison of Upper and Lower Esophageal Regions
Hadijat Makinde¹, Miranda Gurra¹, Salina Dominguez², Matthew Dapas², Tyler Therron², Kathleen Aren³, Marie-Pier Tetreault², Monique Hinchcliff⁴, Deborah Winter⁵ and Harris Perlman¹, ¹Northwestern University, Chicago, IL, ²Northwestern University, Chicago, ³Northwestern University Division of Rheumatology, Chicago, IL, ⁴Yale School of Medicine, Westport, CT, ⁵Northwestern University, Skokie, IL
Background/Purpose: Systemic sclerosis (SSc) is characterized by an initial inflammatory phase followed by fibrosis. Esophageal dysfunction in SSc is associated with gastroesophageal reflux, leading to…
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: 0072 • ACR Convergence 2024
The Association Between Activation of Inflammasome and HLA-B27 in Dendritic Cells of Patients with Axial Spondyloarthritis
Jina Yeo¹, Min-Gang Kim², Hye Eun Lee³, Yeonsoo Yang², Mi Ryoung Seo¹, Hyo-Jin Choi¹, Eun Young Lee⁴, Dae Ho Lee³ and Han Joo Baek⁵, ¹Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea, ²Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea, ³Division of Endocrinology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea, ⁴3Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, ⁵Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Inchon, South Africa
Background/Purpose: Axial spondyloarthritis (axSpA) exhibits a predominant involvement of the innate immune system, marked by abnormal functions of innate immune cell such as dendritic cells…
Abstract Number: 1863 • ACR Convergence 2024
Human Endogenous Retroviruses Promote the Aberrant T Cell Differentiation in Systemic Lupus Erythematosus
Xiaoli Min¹, Jiali Wu², Yaqin Yu³, Qianjin Lu⁴ and Ming Zhao⁴, ¹Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, China (People's Republic), ²Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, China (People's Republic), ³Central South University, Changsha, China (People's Republic), ⁴Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China (People's Republic)
Background/Purpose: Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs and systems. The complex pathogenesis of SLE involved the abnormal activation of CD4+T cells and DNA hypomethylation modification. Human endogenous retroviruses (HERVs)…
Abstract Number: 0305 • ACR Convergence 2024
Inflammatory T Cell Expansion in Yao Syndrome
Danielle Xie¹, Rimanpreet Kaur², Richard Kew², Qingping Yao³ and Charles Vorkas², ¹Stony Brook University, East Setauket, ²Stony Brook University, Stony Brook, ³Stony Brook University, Stony Brook, NY
Background/Purpose: Yao syndrome (YAOS, #OMIM 617321), formerly known as nucleotide-binding oligomerization protein containing 2 (NOD2)-associated autoinflammatory disease, is associated with specific NOD2 mutations and affects…
Abstract Number: 2199 • ACR Convergence 2024
Mycobacterial Infection and Renal and Bladder Malignancy in 2 IFNopathy Patients on High Doses of JAK Inhibitors
Sara Alehashemi¹, Kader Cetin Gedik², Cassandra Calabrese³, Sherry Nguyen⁴, Alexi Baumgardner⁴, Katsiaryna Uss⁴, Kip Friend⁴, Ariane Soldatos⁵, Adriana Almeida de Jesus⁶ and Raphaela Goldbach-Mansky⁷, ¹NIH/NIAID/TADS, Potomac, MD, ²Translational Autoinflammatory Diseases section (TADS), LCIM, NIAID, NIH, Pittsburgh, PA, ³Cleveland Clinic Foundation, Cleveland Heights, OH, ⁴Translational Autoinflammatory Diseases section (TADS), LCIM, NIAID, NIH, Bethesda, MD, ⁵NINDS/NIH, Bethesda, MD, ⁶NIAID, NIH, Silver Spring, MD, ⁷Translational Autoinflammatory Diseases section (TADS), LCIM, NIAID, NIH, Potomac, MD
Background/Purpose: Autoinflammatory Type I Interferonopathies (IFNopathies) include STINGopathies (e.g., SAVI and COPA syndrome), proteasomopathies (e.g., CANDLE/Proteasome associated autoinflammatory syndrome (PRAAS), and oligonucleotidopathies (e.g., AGS: Aicardi-Goutières…

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