Abstracts tagged "B cell tolerance"

Abstract Number: 3 • 2018 ACR/ARHP Annual Meeting
Interferon-Alpha Disrupts DNA-Specific B Cell Tolerance in 3H9 Mice
Dario Ferri¹, Yuriy Baglaenko², Ariana Karanxha¹, Kieran Manion¹, Carolina Grajales¹ and Joan E. Wither¹, ¹Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada, ²Department of Biomedical Informatics, Brigham Women's Hospital, Harvard Medical School, Boston, MA
Background/Purpose: A central mediator of Systemic Lupus Erythematosus (SLE) pathogenesis is interferon-alpha (IFNα), which is elevated in the serum of SLE patients. IFNα has 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: 58 • 2018 ACR/ARHP Annual Meeting
Inhibition of Lipid Phosphatase SHIP1 Expands Myeloid-Derived Suppressor Cells and Attenuates Rheumatoid Arthritis in Mice
Eui Young So¹, Changqi Sun², Patrycja M Dubielecka¹, Anthony M. Reginato³ and Olin D. Liang¹, ¹Division of Hematology/Oncology, Rhode Island Hospital, Providence, RI, ²Division of Rheumatology, Rhode Island Hosital/The Warren Alpert School of Medicine of Brown University, Providence, RI, ³Division of Rheumatology, Rhode Island Hospital, Providence, RI
Background/Purpose: The SH2-containing inositol-5’-phosphatase-1 (SHIP1) controls PI3K initiated signaling by limiting membrane recruitment and activation of AKT. SHIP1 knockout in mice leads to an increase…
Abstract Number: 836 • 2017 ACR/ARHP Annual Meeting
B Cell Receptor Sequencing of Anti-Citrullinated Protein Antibody Expressing B Cells Indicates a Selective Advantage for the Introduction of N-Glycosylation Sites during Somatic Hypermutation
Rochelle D. Vergroesen¹, Linda Slot¹, Lise Hafkenscheid¹, Marvyn T. Koning², Ellen I.H. van der Voort³, Christine A. Grooff¹, George Zervakis², Tom W.J. Huizinga¹, Theo Rispens⁴, Hendrik Veelken², Rene E.M. Toes¹ and Hans U. Scherer³, ¹Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ²Hematology, Leiden University Medical Center, Leiden, Netherlands, ³Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁴Immunopathology, Sanquin Research, Amsterdam, Netherlands
Background/Purpose: The vast majority (>90%) of anti-citrullinated protein antibodies (ACPA) of the IgG isotype in serum and synovial fluid of patients with rheumatoid arthritis carry…
Abstract Number: 2348 • 2017 ACR/ARHP Annual Meeting
A New Cause of Mendelian Lupus Due to IKZF1 Mutation Underlines the B Cell Landscape Heterogeneity in Monogenic Lupus
Alexandre Belot^1,2, Cecile Frachette³, Omarjee Sulliman Ommar², Anne-Laure Mathieu², Thibault Andrieu², Paul Mondier², Gillian Rice⁴, Heloise Reumaux⁵, David Launay^6,7, Marc Lambert^8,9, Guillaume Lefevre¹⁰, Nicole Fabien¹¹, Christophe Malcus¹², Isabelle Rouvet¹³, Emilie Chopin¹³, Anne-Sophie Michallet¹⁴, Thierry Defrance¹⁴, Thierry Walzer¹⁴ and Yanick J Crow¹⁵, ¹Pediatric Rheumatology Unit, HFME, Hospices Civils de Lyon, Bron, France, ²U1111, INSERM, Lyon, France, ³Hospices Civils de Lyon, Bron, France, ⁴Manchester Academic Health Science Centre, Institute of Human Development, University of Manchester, Manchester, United Kingdom, ⁵Pediatric Rheumatology, CHRU Lille, Lille, France, ⁶LIRIC, INSERM UMR 995, Lille, France, ⁷Service de Médecine Interne, Centre National de Référence des Maladies Systémiques Rares, Hôpital Claude Huriez, CHRU Lille, Lille, France, ⁸Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France, Lille, France, ⁹Medecine Interne Lilloise, Service de médecine interne, Hôpital Claude Huriez, Université Lille II, Lille, France, Lille, France, ¹⁰Internal Medicine, Lille University Hospital, Lille, France, ¹¹Immunology Department, UF d'Autoimmunité, Immunology Department, CHU de Lyon HCL- GH Sud, Lyon, France, ¹²Cellular Immunology Department - Laboratoire d'immunologie cellulaire, Groupement Hospitalier Edouard Herriot, Lyon, France, ¹³Cellular Biotechnology Department, Centre de biologie et pathologie Est, Hospices civils de Lyon, Lyon, France, ¹⁴International Center for Infectiology Research - CIRI, Lyon, France, ¹⁵Institut Imagine, Paris, France
Background/Purpose: Next generation sequencing (NGS) represents a revolution in the field of molecular medicine, and offers a new approach to deciphering the pathogenesis of complex…
Abstract Number: 2567 • 2017 ACR/ARHP Annual Meeting
Type I IFN Blockade Restores Normal Transitional B Cell Development Post-Anti-CD20 Depletion
Jennie Hamilton¹, Qi Wu², PingAr Yang³, Bao Luo⁴, Shanrun Liu⁵, Huixian Hong⁶, Jun Li⁷, Hui-Chen Hsu² and John D. Mountz⁸, ¹Medicine/Division of Clinical Immunology and Rhematology, University of Alabama at Birmingham, Birmingham, AL, ²Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ³Department of Medicine, Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ⁴Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ⁵Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, ⁶University of Alabama at Birmingham， Division of Clinical Immunology and Rheumatology, Department of Medicine, Birmingham, AL, ⁷Medicine, University of Alabama at Birmingham, Birmingham, AL, ⁸University of Alabama at Birmingham, Department of Medicine, Birmingham, AL
Background/Purpose: Application of B cell depletion therapy (BCDT) for treatment of SLE has shown promise in some patients, but some patients exhibit disease relapses. Anti-type…
Abstract Number: 23 • 2017 ACR/ARHP Annual Meeting
Auto-Reactive B Cells Escape Peripheral Tolerance Checkpoints in Patients with PR3-ANCA Associated Vasculitis
Divi Cornec¹, Alvise Berti², Amber Hummel¹, Tobias Peikert¹, Jacques-Olivier Pers³ and Ulrich Specks⁴, ¹Mayo Clinic, Rochester, MN, ²Department of Immunology, Rheumatology, Allergy and Rare Diseases, San Raffaele Scientific Institute, Milan, Italy, ³Immunology, Brest University Medical School Hospital, Brest, France, ⁴Mayo Clinic College of Medicine, Rochester, MN
Background/Purpose: While extensive studies have been performed to characterize ANCA, little is known about the auto-reactive B cells that produce these autoantibodies. Indirect evidence previously…
Abstract Number: 831 • 2017 ACR/ARHP Annual Meeting
Interferon-Alpha Disrupts Tolerance in a Mouse Model of B Cell Anergy
Dario Ferri¹, Yuriy Baglaenko², Kieran Manion², Nan-Hua Chang² and Joan E. Wither³, ¹Immunology, University of Toronto, Toronto, ON, Canada, ²Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada, ³Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada
Background/Purpose: Systemic Lupus Erythematosus (SLE) is characterized by the production of anti-nuclear antibodies that deposit within tissues leading to organ damage. A central mediator of…
Abstract Number: 832 • 2017 ACR/ARHP Annual Meeting
Single Cell Analysis Reveals Heterogeneity of Type I IFN Gene Expression in Developing Autoreactive B Cells
Jennie Hamilton¹, PingAr Yang², Qi Wu³, Bao Luo⁴, Shanrun Liu⁵, Jun Li⁶, Mark Walter⁷, Eleanor Fish⁸, Hui-Chen Hsu³ and John D. Mountz⁹, ¹Medicine/Division of Clinical Immunology and Rhematology, University of Alabama at Birmingham, Birmingham, AL, ²Department of Medicine, Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ³Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ⁴Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ⁵Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, ⁶Medicine, University of Alabama at Birmingham, Birmingham, AL, ⁷Microbiology, University of Alabama at Birmingham, Birmingham, AL, ⁸University Health Network & Department of Immunology, University of Toronto, Toronto General Research Institute, Toronto, ON, Canada, ⁹University of Alabama at Birmingham, Department of Medicine, Birmingham, AL
Background/Purpose: B cell development involves passage through a formative transitional B cell stage in the spleen. In SLE, self-nucleic acid reactive B cells fail to…
Abstract Number: 833 • 2017 ACR/ARHP Annual Meeting
Chronic Cutaneous Lupus Erythematosus Patients Have a Breakdown in Autoreactive VH4.34 Antibody Tolerance While Maintaining Tolerance to dsDNA and Chromatin
Scott Jenks¹, Regina Bugrovsky¹, Xiaoqian Wang^1,2, Aisha Hill³, Chungwen Wei⁴, S. Sam Lim⁵, Ignacio Sanz⁶ and Cristina Drenkard⁵, ¹Emory University School of Medicine and Lowance Center for Human Immunology, Atlanta, GA, ²Division of Rheumatology and Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA, ³Medicine, Emory University School of Medicine, atlanta, GA, ⁴Medicine, Emory University School of Medicine, Atlanta, GA, ⁵Division of Rheumatology, Emory University School of Medicine, Atlanta, GA, ⁶Rheumatology and Lowance Center for Human Immunology, Emory University School of Medicine and Lowance Center for Human Immunology, Atlanta, GA
Background/Purpose: While the contribution of humoral immunity to SLE is well established, the role it plays in chronic cutaneous lupus erythematosus (CCLE) is less clear.…
Abstract Number: 918 • 2016 ACR/ARHP Annual Meeting
Anergic B Cells May Preserve Peripheral Tolerance in Lupus-Prone Congenic Mice
Kieran Manion^1,2, Yuriy Baglaenko^1,2, Nan-Hua Chang², Nafiseh Talaei³ and Joan Wither⁴, ¹Immunology, University of Toronto, Toronto, ON, Canada, ²Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada, ³Genetics and Development, Krembil Research Institute, Toronto, ON, Canada, ⁴Krembil Research Institute, University Health Network, Toronto, ON, Canada
Background/Purpose: Anergic autoreactive B cells are thought to play a critical role in systemic lupus erythematosus (SLE), a chronic autoimmune disease where breach of tolerance…
Abstract Number: 1084 • 2016 ACR/ARHP Annual Meeting
Antibodies to Native Vimentin in Lupus: Characterization, Isotypes, Origins, and Associations with Other Autoimmune Pathways
Andrew Kinloch¹, Yuta Asano¹, Rene Bermea², Kichul Ko², Carole Henry¹, Nirit Mor-Vaknin³, David Markovitz⁴, Patrick Wilson¹ and Marcus R. Clark⁵, ¹Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, ²Medicine, University of Chicago, Chicago, IL, ³Infectious Diseases, University of Michigan, Ann Arbor, MI, ⁴Internal Medicine, University of Michigan, Ann Arbor, MI, ⁵Rheumatology and Knapp Center for Lupus Research, University of Chicago, Chicago, IL
Background/Purpose: Severe lupus tubulointerstitial nephritis (TIN) is prognostic of renal failure and characterized by tertiary lymphoid organogenesis. We have previously demonstrated that the dominant target…
Abstract Number: 1086 • 2016 ACR/ARHP Annual Meeting
Analysis of the Naive B Cell Repertoire in Belimumab Treated SLE Patients
Weiqing Huang¹, Cynthia Aranow², Cosmin Dascalu¹, Richard Furie³ and Anne Davidson⁴, ¹Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, NY, ²The Feinstein Institute for Medical Research, Manhasset, NY, ³Division of Rheumatology, North Shore LIJ Health System, Great Neck, NY, ⁴Autoimmunity and Musculoskeletal Diseases, Feinstein Inst for Med Rsch, Manhasset, NY
Background/Purpose: BAFF is a TNF-like cytokine that supports the survival and differentiation of B cells. The anti-BAFF antibody belimumab is the only new drug that…
Abstract Number: 1089 • 2016 ACR/ARHP Annual Meeting
Decreased B Cell Activation-Induced Apoptosis in Cells Overexpressing Interferon Regulatory Factor 5 (IRF5), a Gene Associated with Risk for Systemic Lupus Erythematosus and Other Autoimmune Diseases
Brian Poole¹, Caleb Cornaby², Kalare Eberting², Wesley Cheney², Grant Walker², Craig Smith², Tosh Dowling² and Emily Mello², ¹Brigham Young University, Provo, UT, ²Microbiology and Molecular Biology, Brigham Young University, Provo, UT
Background/Purpose: The transcription factor Interferon Regulatory Factor 5 (IRF5) plays a crucial role in the functioning of several cell types such as macrophages, dendritic, and…
Abstract Number: 2114 • 2016 ACR/ARHP Annual Meeting
Exposure to Carbamylated Self- and Non-Self-Proteins Can Lead to a Break-of -Tolerance and the Induction of Autoimmunity
Jacqueline Dekkers¹, Marije K. Verheul², Jeroen Stoop³, Bisheng Liu⁴, Peter A. van Veelen⁵, Martin Hegen⁶, Stephen Rapecki⁷, Tom WJ Huizinga², Leendert A. Trouw⁴ and René Toes⁴, ¹Rheumatology, Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands, ²Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ³Leiden University Medical Center (LUMC), Leiden, Netherlands, ⁴Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁵Immunohematology and Bloodbank, Leiden University Medical Center, Leiden, Netherlands, ⁶Inflammation, Wyeth Pharmaceuticals, Cambridge, MA, ⁷UCB Pharma, Slough, United Kingdom
Background/Purpose: Autoantibodies are an important hallmark of Rheumatoid Arthritis (RA). Approximately 50% of RA patients harbor anti-carbamylated protein (CarP) antibodies. These autoantibodies target proteins that…

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