Abstracts tagged "interferons"

Abstract Number: 1663 • 2017 ACR/ARHP Annual Meeting
De Novo Mutation in ΑCΑCΒ in Childhood Onset SLE Highlights a Novel Role As Modulator of Nucleic Acid Sensor-Driven Type I Interferon Responses
Isaac Harley¹, Hanna Schulz¹, John Cambier², Leah C. Kottyan³, John B. Harley⁴, V. Michael Holers⁵, Hermine I. Brunner⁶, Kristine Kuhn¹, Kevin D. Deane¹ and Kenneth Kaufman⁷, ¹Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, ²Deparment of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO, ³Center for Autoimmune Genomics and Etiology (CAGE), Division of Allergy and Immunology, Cincinnati Children's Hospital, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁴Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁵Medicine, Division of Rheumatology, University of Colorado Denver, Aurora, CO, ⁶Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁷Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center; US Department of Veterans Affairs Medical Center, Cincinnati, OH
Background/Purpose: Rare variants provide important opportunity for mechanistic insight as they carry substantial effect sizes and provide deep insight into disease etiopathogenesis. To date, several…
Abstract Number: 1719 • 2017 ACR/ARHP Annual Meeting
Accelerated Wound Healing in Megakaryocyte/Platelet-Specific Fli1 Knockout Mice Due to the up-Regulated Expression of Interferon-γ
Megumi Hirabayashi¹, Yoshihide Asano², Takashi Yamashita¹, Ryosuke Saigusa¹, Shunsuke Miura³, Kouki Nakamura¹, Takuya Miyagawa¹, Takashi Taniguchi¹, Ayumi Yoshizaki¹ and Shinichi Sato⁴, ¹Dermatology, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, ²Applied Chemistry, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, ³University of Tokyo, Graduate School of Medicine, Tokyo, Japan, ⁴Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
Background/Purpose: Fli1 deficiency, a potential predisposing factor of systemic sclerosis (SSc), induces SSc-like phenotypes in dermal fibroblasts, endothelial cells, keratinocytes, and macrophages. However, it is…
Abstract Number: 1893 • 2017 ACR/ARHP Annual Meeting
Pharmacokinetics (PK), Pharmacodynamics (PD), and Proposed Dosing of Oral Janus Kinase (JAK)1 and JAK2 Inhibitor Baricitinib in Patients with IFN-Mediated Autoinflammatory Diseases (AIDs)
Hanna Kim¹, Kristina M. Brooks², Paul Wakim³, Mary Blake⁴, Stephen R. Brooks⁵, Gina A. Montealegre Sanchez⁶, Adriana Almeida de Jesus⁶, Yan Huang⁶, Wanxia Li Tsai⁷, Massimo G. Gadina⁴, Parag Kumar² and Raphaela Goldbach-Mansky⁶, ¹Pediatric Translational Research Branch, NIAMS/NIH, Bethesda, MD, ²Clinical Pharmacokinetics Research Unit, Pharmacy Department, NIH Clinical Center, Bethesda, MD, ³Biostatistics and Clinical Epidemiology Service, NIH Clinical Center, Bethesda, MD, ⁴Translational Immunology Section, Office of Science and Technology, NIAMS/NIH, Bethesda, MD, ⁵Biodata Mining and Discovery Section, Office of Science and Technology, NIAMS/NIH, Bethesda, MD, ⁶Translational Autoinflammatory Disease Studies (TADS), Laboratory of Clinical Investigation and Microbiology (LCIM), NIAID/NIH, Bethesda, MD, ⁷Translational Immunology, Office of Science and Technology, NIAMS/NIH, Bethesda, MD
Background/Purpose: JAK inhibitors reduce IFN-signaling ex vivo. We evaluated the PK and PD of the oral JAK1 and JAK2 inhibitor, baricitinib, from data collected in…
Abstract Number: 2336 • 2017 ACR/ARHP Annual Meeting
Expression of Myxovirus-Resistance Protein a: A Possible Marker of Muscular Disease Activity in Juvenile Dermatomyositis
Sirisucha Soponkanaporn¹, Claire Deakin², Lucy Marshall², Cerise Johnson², Peter Schutz¹ and Lucy R Wedderburn², ¹Infection Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, University College London, United Kingdom, London, United Kingdom, ²Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, University College London, United Kingdom, London, United Kingdom
Background/Purpose: Juvenile dermatomyositis (JDM) is a chronic autoimmune myopathy characterized by proximal muscle weakness and typical skin rashes. Type I interferon (IFN) gene expression in…
Abstract Number: 2568 • 2017 ACR/ARHP Annual Meeting
Prophylactic and Therapeutic Administration of a JAK1-Selective Inhibitor Blocks and Reverses Nephritis and Sialadenitis in NZB/W-F1 Mice
Rachel Twomey¹, Stuart Perper¹, Susan Westmoreland¹, Terry Melim¹, Soumya Mitra¹, Zheng Liu¹, Manuel Duval¹, Carolyn Cuff², Andrew Long¹, Anthony Slavin² and Stephen Clarke¹, ¹AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA, ²Immunology Discovery, AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA
Background/Purpose: Signaling of most cytokine receptors occurs through the JAK-STAT pathway. This is true of cytokines linked to the etiology of systemic lupus erythematosus (SLE)…
Abstract Number: 2589 • 2017 ACR/ARHP Annual Meeting
Functional and Mechanistic Characterization of Anifrolumab, a Fully Human Monoclonal Antibody Targeting the Interferon Alpha Receptor 1 for the Treatment of SLE
Gary P. Sims¹, Jeffrey Riggs², Richard Hanna¹, Bhargavi Rajan³, Jodi Karnell¹, Kamelia Zerrouki¹, Divya Sagar¹, Inna Vainshtein³, Erika Farmer⁴, Meina Liang³, Miguel A. Sanjuan¹ and Roland Kolbeck¹, ¹Respiratory, Inflammation and Autoimmunity (RIA), MedImmune, LLC, Gaithersburg, MD, ²Respiratory, Inflammation and Autoimmunity (RIA), MedImmune LLC, Gaithersburg, MD, ³MedImmune, LLC, Mountain View, CA, ⁴Analytical Sciences, MedImmune, LLC, Gaithersburg, MD
Background/Purpose: Increased type I interferon (IFN) activity is associated with the pathogenesis of SLE. Anifrolumab, a fully human immunoglobulin (Ig) G1 κ monoclonal antibody in clinical…
Abstract Number: 2592 • 2017 ACR/ARHP Annual Meeting
Safety, Tolerability, and Pharmacokinetics of Subcutaneous and Intravenous Anifrolumab in Healthy Volunteers
Raj Tummala¹, Tomas Rouse², Anna Berglind² and Linda Santiago³, ¹AstraZeneca, Gaithersburg, MD, ²AstraZeneca, Gothenberg, Sweden, ³MedImmune, LLC, Mountain View, CA
Background/Purpose: Anifrolumab is a fully human anti–interferon-ɑ receptor 1 monoclonal antibody in Phase III development as an intravenous (IV) therapeutic for systemic lupus erythematosus (SLE).…
Abstract Number: 2601 • 2017 ACR/ARHP Annual Meeting
Novel Anti-Malarial Drug Derivative Inhibited Type I Interferon Production and Autoimmune Inflammation in SLE Patient PBMC and in Trex1-/- Mouse Spleen and Heart
Jie An¹, Weinan Lai^2,3, Joshua Woodward⁴, Xizhang Sun¹, Lena Tanaka¹, Tomikazu Sasaki⁵ and Keith B. Elkon⁶, ¹Division of Rheumatology, University of Washington, Seattle, WA, ²Department of Medicine/Division of Rheumatology, University of Washington, Seattle, WA, ³Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China, ⁴Department of Microbiology, University of Washington, Seattle, WA, ⁵Department of Chemistry, University of Washington, Seattle, WA, ⁶Division of Rheumatology, Department of Medicine, University of Washington, Seattle, WA
Background/Purpose: Type I interferon (IFN-I) is strongly implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) as well as rare monogenic ‘interferonopathies’ such as Aicardi-Goutieres…
Abstract Number: 2816 • 2017 ACR/ARHP Annual Meeting
Prediction of Connective Tissue Disease in an at-Risk Cohort Using a Novel Interferon Stimulated Gene Expression Score
Md Yuzaiful Md Yusof^1,2, Yasser M El-Sherbiny^1,3, Antonios Psarras¹, Elizabeth M.A. Hensor^1,4, Adewonuola Alase¹, Alaa Mohamed¹, Miriam Wittmann^1,4, Paul Emery^1,4 and Edward M Vital^1,4, ¹Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, ²NIHR Leeds Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, ³Clinical Pathology dept., School of Medicine, Mansoura University, Mansoura, Egypt, ⁴NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
Prediction of connective tissue disease in an at-risk cohort using a novel interferon stimulated gene expression scoreBackground/Purpose: A period of ANA positivity and other immune…
Abstract Number: 2828 • 2017 ACR/ARHP Annual Meeting
A Graph-Theoretic-Approach Applied to Modular-Repertoire-Analysis Identifies Shared Gradual Whole Blood Interferon Signatures in Systemic Lupus Erythematosus and Primary Sjögren’s Syndrome Patients and Reveals New Interferon-Related Modules in Disease Progression
Ilya Korsunski¹, Noémie Jourde-Chiche², Peter Gregersen³, Damien Chaussabel⁴, Laurent Chiche⁵ and Naomi I. Maria⁶, ¹Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, NY, ²Nephrology, AP-HM, Department of Nephrology, CHU Conception, Marseille, France, ³Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Med Res, Manhasset, NY, ⁴Translational Medicine, Sidra Medical and Research Center, Doha, Qatar, ⁵Internal medicine, Hopital europeen, Marseille, France, ⁶Center for Autoimmune and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, NY
Background/Purpose: There is significant clinical and molecular heterogeneity among patients suffering from systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and primary Sjögren’s Syndrome…
Abstract Number: 3220 • 2016 ACR/ARHP Annual Meeting
Distinct Single Cell Gene Expression Signatures of Monocyte Subsets Differentiate Between TNF-Alpha Inhibitor Treatment Response Groups in Rheumatoid Arthritis
Theresa L. Wampler Muskardin¹, Wei Fan², Zhongbo Jin³, Mark A. Jensen⁴, Jessica M. Dorschner³, Yogita Ghodke-Puranik³, Kerry Wright¹, John M. Davis III⁵, Eric L. Matteson¹, Clement Michet Jr.¹, Thomas G. Mason II⁶, Scott T. Persellin⁷, Daniel Schaffer¹, Betty Dicke¹, Danielle Vsetecka³ and Timothy B. Niewold⁸, ¹Rheumatology, Mayo Clinic, Rochester, MN, ²Mayo Clinic, Rochester, MN, ³Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, ⁴Department of Immunology and Division of Rheumatology, Mayo Clinic, Rochester, MN, ⁵Division of Rheumatology, Mayo Clinic, Rochester, MN, ⁶Division of Rheumatology - Department of Medicine, Mayo Clinic Rochester, Rochester, MN, ⁷Department of Rheumatology, Mayo Clinic Rochester, Rochester, MN, ⁸Rheumatology and Immunology, Mayo Clinic, Rochester, MN
Background/Purpose: In rheumatoid arthritis (RA), initiating effective treatment as soon as possible within the so-called therapeutic “window of opportunity” is the strategy, and remission is…
Abstract Number: 761 • 2016 ACR/ARHP Annual Meeting
Exposure-Response Analysis for Selection of Optimal Dosage Regimen of Anifrolumab in Patients with Systemic Lupus Erythematosus
L Santiago¹, B Wang², P Brohawn², L Wang², G Illei² and L Roskos², ¹MedImmune, Mountain View, CA, ²MedImmune, Gaithersburg, MD
Background/Purpose: Anifrolumab is a fully human IgG1 monoclonal antibody directed against subunit 1 of the type I interferon–α receptor (IFNAR1) currently in development for the…
Abstract Number: 774 • 2016 ACR/ARHP Annual Meeting
BIIB059, an Anti-BDCA2 Monoclonal Antibody, Demonstrates Acceptable Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamic (PD) Effects in a Phase 1 Study with Single Ascending Doses (SAD) in Healthy Volunteers
David Martin, Lauren Stevenson, Pratapa Prasad, Karen Smirnakis, Amy Kao, Dania Rabah, Wenting Wang and Nathalie Franchimont, Biogen, Cambridge, MA
Background/Purpose: Type I interferons (IFN-I) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). In SLE, immune complexes stimulate plasmacytoid dendritic cells (pDCs) to…
Abstract Number: 792 • 2016 ACR/ARHP Annual Meeting
Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] Response Is Associated with Global Benefit in Patients with Moderate to Severe SLE
R Furie¹, L Wang², J Drappa² and G Illei², ¹Northwell Health, Great Neck, NY, ²MedImmune, Gaithersburg, MD
Background/Purpose: Post-hoc analysis of two Phase III studies of belimumab1 showed that an SRI(4) response is associated with clinically meaningful benefits, irrespective of treatment assignment.…
Abstract Number: 864 • 2016 ACR/ARHP Annual Meeting
Takayasu Arteritis Developed over the Age of 40 Has Lower Levels of Interferon Gamma and Interleukin 17 at Disease Onset and Fewer Subsequent Relapses
Shoichi Fukui¹, Naoki Iwamoto², Toshimasa Shimizu², Masataka Umeda², Ayako Nishino³, Yoshiro Horai², Tomohiro Koga⁴, Shin-ya Kawashiri⁵, Kunihiro Ichinose¹, Yasuko Hirai², Mami Tamai¹, Hideki Nakamura⁵, Tomoki Origuchi⁶, Kiyoshi Migita⁷, Yukitaka Ueki⁸ and Atsushi Kawakami⁹, ¹Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ²Department of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan, ³Department of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki Universit, Nagasaki, Japan, ⁴Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁵Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁶Department of Rehabilitation Sciences, Nagasaki University, Nagasaki, Japan, ⁷Department of Rheumatology and Clinical Research Center, Nagasaki Medical Center, Omura, Japan, ⁸Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Japan, ⁹Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Background/Purpose: The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis (TAK) include age at disease onset ≤ 40 years. We aimed…

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