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  • Abstract Number: 8 • 2018 ACR/ARHP Annual Meeting

    Repertoire Studies in Rheumatoid Arthritis Reveal B-Cell Distortions and Baseline Shifts in Unmutated IgG

    Yan Wang1, Katy A. Lloyd2, Sunithi Gunasekera3, Camilla Eriksson3, Daniel Ramsköld2, Karin Lundberg4, Per-Johan Jakobsson1, Ulf Göransson3, Vivianne Malmström1 and Caroline Grönwall5, 1Rheumatology Unit, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden, 2Rheumatology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden, 3Division of Pharmacognosy, Dept. of Medicinal Chemistry, Uppsala University, Uppsala, Sweden, 4Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 5Dep. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden

    Background/Purpose: The immunological hallmark of rheumatoid arthritis (RA) is autoreactivity to citrullinated proteins and rheumatoid factor activity. Hence, the adaptive immune system and B cells…
  • Abstract Number: 9 • 2018 ACR/ARHP Annual Meeting

    Integration of Cytokine Profiles with Distinct B-Cell Functions Reveals a Specific Micro-Environmental Framework in Autoimmune Diseases

    Quentin Simon1, Alexis Grasseau2, Bénédicte Rouvière2, Laetitia Le Pottier2, Divi Cornec3, Maria Orietta Borghi4, Rocio Aguilar Quesada5, Yves Renaudineau2,6, Marta Alarcón-Riquelme7, Jacques-Olivier Pers1 and Sophie Hillion2,6, 1U1227, Université de Brest, Inserm, Labex IGO, CHU de Brest, Brest, France, 2U1227, Lymphocytes B et Autoimmunité, Université de Brest, Inserm, Brest, France, 3Hopital La Cavale Blanche, Brest, France, 4University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy, 5Biobanco Del Sistema Sanitario Publico de Andalucía, Sevilla, Spain, 6CHU de Brest, Brest, France, 7Medical Genomics, Center for Genomics and Oncological Research (GENYO), Granada, Spain

    Background/Purpose: The functional duality of B cells is central to balance immune homeostasis by regulating or promoting the immune response. However, the mechanisms by which…
  • Abstract Number: 10 • 2018 ACR/ARHP Annual Meeting

    Fibroblast like Synoviocytes (FLS) Are Capable of Inducing Phenotypical Changes Including Class Switch Recombination (CSR) in Naive B Cells, but Additional Factors Are Required to Trigger Immunoglobulin Secretion

    Dennis Bleck1, Torsten Lowin2, Matthias Schneider3 and Georg Pongratz4, 1Rheumatology Policlinic & Hiller Research Unit, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany, 2Department and Hiller Research Center for Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany, 3Department and Hiller Research Center for Rheumatology, Heinrich-Heine University, Duesseldorf, Germany, 4Dpt. of Rheumatology - Hiller Research Center Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany

    Background/Purpose: Rheumatoid Arthritis (RA) is a disease characterized by chronic inflammation of the synovial tissue in joints. It is driven by highly activated B cells.…
  • Abstract Number: 11 • 2018 ACR/ARHP Annual Meeting

    PAD4-Independent Interaction of ACPA with Nuclear Antigens in Apoptotic Cells and Neutrophil Extracellular Traps (NETs) Defines a Subset of Autoantibodies

    Gustaf Wigerblad1, Katy A. Lloyd1, Peter Sahlström2, Karine Chemin2, Johanna Steen2, Philip J. Titcombe2,3, Diana Zhou2, Ragnhild Stålesen1, Bianka Marklein4, Elena Ossipova2, Johan Rönnelid5, Luca Piccoli6, Antonio Lanzavecchia6, Daniel L. Mueller3, Karl Skriner4, Lars Klareskog2, Fredrik Wermeling1, Vivianne Malmström2 and Caroline Grönwall7, 1Rheumatology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden, 2Rheumatology Unit, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden, 3The Center for Immunology, Dept. of Medicine, University of Minnesota Medical School, Minneapolis, MN, 4Dept. of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany, 5Dept. of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden, 6Università della Svizzera italiana, Institute for Research in Biomedicine, Bellinzona, Switzerland, 7Dep. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden

    Background/Purpose: Rheumatoid arthritis (RA) associated anti-citrullinated protein autoantibodies (ACPA) bind a wide range of citrullinated proteins with high cross-reactivity. Recent findings suggest that certain, but…
  • Abstract Number: 12 • 2018 ACR/ARHP Annual Meeting

    Protein Phosphatase 2A, a Serine/Threonine Phosphatase, Is Essential for Optimal B Cell Function

    Esra Meidan1, Hao Li2, Christina Ioannidis3, Wenliang Pan3, Noe Rodriguez Rodriguez4, Jose Crispin4, Sokratis Apostolidis5, John Manis6, Amir Sharabi7, Maria G. Tsokos3 and George C Tsokos8, 1Division of Immunology, Boston Children's Hospital, Boston, MA, 2Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 3Beth Israel Deaconess Medical Center, Boston, MA, 4Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico, 5Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 6Boston Children's Hospital, Boston, MA, 7Department of Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA, 8Division of Rheumatology, Department of Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, Boston, MA

    Background/Purpose: Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase ubiquitously expressed in eukaryotic cells. PP2A levels and activity are increased in T cells from patients…
  • Abstract Number: 13 • 2018 ACR/ARHP Annual Meeting

    Shared Genetic Origins Among Anti-Proteinase 3 and Anti-Glomerular Basement Membrane Double-Positive Human Autoantibodies

    Jeffrey R. Ord1, Amy G. Clark1 and Mary H. Foster2, 1Duke University Medical Center, Durham, NC, 2Medicine, Duke University Medical Center, Durham, NC

    Background/Purpose: Patients with ANCA vasculitis and anti-glomerular basement membrane (GBM) nephritis (Goodpasture’s Disease) develop pathogenic autoantibodies (autoAb) that destroy the microvasculature in lungs and kidneys.…
  • Abstract Number: 14 • 2018 ACR/ARHP Annual Meeting

    Individual RA-Derived Monoclonal Anti-Citrullinated Protein Autoantibodies (ACPA) Have Extensive Citrulline Multi-Reactivity Demonstrated By a Large-Scale Protein Array Platform

    Peter Sahlström1, Johanna Steen1, Madeleine Jenning2, Philip J. Titcombe1,3, Ute Nonhoff4,5, Ragnhild Stålesen6, Bianka Marklein2, Daniel L. Mueller3, Zoltan Konthur4, Karin Lundberg7, Anca I. Catrina6, Lars Klareskog1, Vivianne Malmström1, Karl Skriner2 and Caroline Grönwall8, 1Rheumatology Unit, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden, 2Dept. of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany, 3The Center for Immunology, Dept. of Medicine, University of Minnesota Medical School, Minneapolis, MN, 4Engine GmbH, Hennigsdorf, Germany, 5Max Planck Institute of Colloids and Interfaces, Potsdam, Germany, 6Rheumatology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden, 7Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 8Dep. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden

    Background/Purpose: The presence of serum IgG anti-citrullinated protein autoantibodies (ACPA) in rheumatoid arthritis (RA), is associated with more aggressive disease progression. Although ACPA have been…
  • Abstract Number: 15 • 2018 ACR/ARHP Annual Meeting

    Abnormal ZAP-70 Expression in B Cells: New Potential Role in Tolerance Breakdown

    Mickaël Martin1, Anne-marie KNAPP1, Dana GHERGUS1, Fabien DELMOTTE2, Laurent Vallat3, Cédric SCHLEISS3, Raoul HERBRECHT4, Anne-sophie KORGANOW1, Frédéric GROS1, Sophie JUNG1, Pauline SOULAS-SPRAUEL1, Eric Meffre2 and Thierry Martin5, 1CNRS UPR 3572 "Immunopathology and Therapeutic Chemistry"/Laboratory of Excellence Medalis, Institute of Molecular and Cellular Biology (IBMC), STRASBOURG, France, 2Department of Immunobiology, Yale University School of Medicine, NEW HAVEN, CT, 3Laboratoire d'hematologie, Hopital Hautepierre, STRASBOURG, France, 4Service d'Hématologie et Oncologie, Hôpitaux universitaires de Strasbourg, STRASBOURG, France, 5CNRS UPR 3572 "Immunopathology and Therapeutic Chemistry"/Laboratory of Excellence Medalis, Institute of Molecular and Cellular Biology (IBMC), STRSBOURG, France

    Background/Purpose: Abnormal expression of the tyrosine kinase ZAP-70 by tumoral B cells in chronic lymphocytic leukemia (CLL) is associated with B cell receptor (BCR) hypersignalling…
  • Abstract Number: 16 • 2018 ACR/ARHP Annual Meeting

    Comprehensive Antibody Profiling Using High Density Peptide Arrays Reveals Novel Citrullinated Protein Targets in Rheumatoid Arthritis Serum Samples

    Ken Lo1, Hanying Li2, Eric Sullivan2 and Jigar Patel2, 1Technology Innovation, Roche Sequencing Solutions - Madison, Madison, WI, 2Roche Sequencing Solutions - Madison, Madison, WI

    Background/Purpose: Autoantibodies against citrullinated proteins are found in 64-89% of rheumatoid arthritis (RA) patients, with a specificity of 88-99%. While citrullinated vimentin, fibrin and histone…
  • Abstract Number: 17 • 2018 ACR/ARHP Annual Meeting

    Kappa-Deleting Recombination Excision Circles (KREC) in B Cells and Serum B Cell Activating Factor (BAFF): Possible Aids in Predicting Juvenile Dermatomyositis Response to Rituximab

    Amer khojah1,2, Victoria Hans3, Wilfredo Marin4, Gabrielle A. Morgan4 and Lauren M. Pachman5,6,7, 1Division of Pediatric Rheumatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 2Division of Pediatric Allergy Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 3Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 4Cure JM Program of Excellence in Myositis Research, Stanley Manne Children’s Research Institute, affiliated with Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 5Cure JM Program of Excellence in Juvenile Myositis Research, Stanley Manne Children’s Research Institute, affiliated with Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 6Pediatric Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 7Rheumatology/Immunology, Ann & Robert H. Lurie Children's Hosptial of Chicago, Chicago, IL

    Background/Purpose: Rituximab is used for the treatment of juvenile dermatomyositis (JDM) with variable success. Some of this variability is presumed to be related to the…
  • Abstract Number: 18 • 2018 ACR/ARHP Annual Meeting

    Cytoplasmic FOXO1 Identifies Novel Disease-Activity Associated B Cell Subsets in SLE

    Molly Hritzo1 and Amit Golding2, 1Microbiology and Molecular Immunology, University of Maryland School of Medicine, Baltimore, MD, 210 South Pine Street, Baltimore VA/VAMHCS AND University of Maryland School of Medicine, Baltimore, MD

    Background/Purpose: A key integrator of external stimuli in lymphocytes, Forkhead box protein O1 (FOXO1) is a highly attractive factor to study in SLE because it…
  • Abstract Number: 19 • 2018 ACR/ARHP Annual Meeting

    Citrulline-Multispecific B Cell Receptor Clades in Rheumatoid Arthritis

    Philip J. Titcombe1,2, Natalie Sippl3, Monika Hansson4, Lena Israelsson3, Khaled Amara3, Timothy B. Niewold5, Lars Klareskog2, Vivianne Malmström2 and Daniel L. Mueller6, 1The Center for Immunology, Dept. of Medicine, University of Minnesota Medical School, Minneapolis, MN, 2Rheumatology Unit, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden, 3Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 4Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, 5Colton Center for Autoimmunity, New York University, New York, NY, 6Medicine/Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN

    Background/Purpose: Anti-citrullinated protein antibodies (ACPA) have proven highly useful as biomarkers in rheumatoid arthritis (RA) and appear to be important to disease pathogenesis. Nevertheless, the…
  • Abstract Number: 20 • 2018 ACR/ARHP Annual Meeting

    Expression and Functions of the Transcription Factors Ikaros and Aiolos in Sjogren’s Syndrome and Systemic Lupus Erythematosus

    Felice Rivellese1,2, Daniele Mauro1, Mattia Congia3, Elena Pontarini1, Peter Schafer4, Michele Bombardieri1,2, Costantino Pitzalis1,5 and Myles J. Lewis1,2, 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, London, United Kindgdom, London, United Kingdom, 2Barts Health NHS Trust & Barts and the London School of Medicine & Dentistry, London, United Kingdom, London, United Kingdom, 3Rheumatology and Rheumatology Unit, University Clinic and AOU of Cagliari, Cagliari, Italy, Cagliari, Italy, 4Celgene Corporation, Summit, NJ, 5Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom

    Background/Purpose: Polymorphisms of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), which are essential for the maturation, differentiation and survival of B cells, have been…
  • Abstract Number: 21 • 2018 ACR/ARHP Annual Meeting

    Elevated EPSTI1 Promote B Cells Hyperactivation through NF-Kb Signaling in Patients with Sjögren ’s Syndrome

    Jin-Lei Sun1, Zhi-Lei Chen2, Chao-Feng Lian3, Ti-Hong Shao2, Hao-Ze Zhang2, Hua Chen3 and Feng-Chun Zhang2, 1Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China, 2Peking Union Medical College Hospital, Beijing, China, 3Rheumatology, Peking Union Medical College Hospital, Beijing, China

    Background/Purpose: Sjogren's syndrome (SS) is a common systemic autoimmune disease characterized with aberrant B cells activation. B cells play a key role in the pathogenesis…
  • Abstract Number: 22 • 2018 ACR/ARHP Annual Meeting

    Monoclonal Anti-Citrullinated Protein Antibodies Generated from RA-Derived B Cells Recognize Amino Acid Motifs Rather Than Specific Proteins

    Johanna Steen1, Philip J. Titcombe2, Bjorn Forsström3, Caroline Grönwall4, Anca I. Catrina5, Daniel Lightwood6, Peter Nilsson7, Lars Klareskog1 and Vivianne Malmström1, 1Rheumatology Unit, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden, 2The Center for Immunology, Dept. of Medicine, University of Minnesota Medical School, Minneapolis, MN, 3SciLifeLab, Royal Technology Highschool,, Stockholm, Sweden, 4Dep. of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden, 5Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, 6Antibody-discovery, UCB-Celltech, Slough, United Kingdom, 7Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden, Stockholm, Sweden

    Background/Purpose: Rheumatoid arthritis (RA) associated anti-citrullinated protein autoantibodies (ACPA) develop before RA diagnosis, at which point a wide range of citrullinated proteins have been shown…
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