ACR Meeting Abstracts

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  • Abstract Number: 1105 • 2015 ACR/ARHP Annual Meeting

    The IgG/IgG4 mRNA Ratio By Quantitative PCR Accurately Diagnoses IgG4-Related Disease and Predicts Treatment Response

    Lowiek Hubers1, Marieke Doorenspleet2, Paulus Klarenbeek3, Emma Culver4, Lucas Maillette de Buy Wenniger5, Roger Chapman4, Stan Van de Graaf6, Joanne Verheij7, Thomas Van Gulik8, Frank Baas9, Ellie Barnes4, Ulrich Beuers1 and Niek De Vries3, 1Dept. of Gastroenterology & Hepatology and Tytgat Institute of Liver and Intestinal Research, Dept. of Gastroenterology & Hepatology and Tytgat Institute of Liver and Intestinal Research, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 2Dept. of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center | Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 3Dept. of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 4Translational Gastroenterology Unit and NDM Oxford University, Translational Gastroenterology Unit and NDM Oxford University, John Radcliffe Hospital/Oxford University, Oxford, United Kingdom, 51Dept. of Gastroenterology & Hepatology and Tytgat Institute of Liver and Intestinal Research, Dept. of Gastroenterology & Hepatology and Tytgat Institute of Liver and Intestinal Research, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 6Dept. of Gastroenterology & Hepatology and Tytgat Institute of Liver and Intestinal Research,, Dept. of Gastroenterology & Hepatology and Tytgat Institute of Liver and Intestinal Research, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 7Dept. of Pathology, Dept. of Pathology, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 8Dept. of Surgery, Dept. of Surgery, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 9Dept. of Genome Analysis, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands

    Background/Purpose : IgG4-associated cholangitis (IAC) and autoimmune pancreatitis (AIP) are major manifestations of IgG4-related disease (IRD). Misdiagnosis and inadequate treatment are common since IAC and…
  • Abstract Number: 1106 • 2015 ACR/ARHP Annual Meeting

    Efficacy of Abbv-105, a Selective and Irreversible Inhibitor of Bruton’s Tyrosine Kinase (BTK), in Multiple Models of Inflammation

    Christian Goess1, Candace Graff2, Ting Ting Zhang2, Gregory Preston2, Richard McCarthy1, Matthew Perham1, Jacqueline Loud1, Christopher M. Harris1, Sara Murdock1, Erik Sampson3, Michael Hoemann4, Michael Friedman4, Robert Talanian3, Jeremy Edmunds4 and Andrew Long1, 1Immunology Pharmacology, AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA, 2DMPK, AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA, 3AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA, 4Chemistry, AbbVie Inc, AbbVie Bioresearch Center, Worcester, MA

    Background/Purpose: Bruton’s Tyrosine Kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling pathways downstream of several key immunoreceptors, including the B cell receptor,…
  • Abstract Number: 1107 • 2015 ACR/ARHP Annual Meeting

    Inhibition of B Cell Activation and Plasma Cell Differentiation By Epratuzumab, a Humanized Monoclonal Antibody Targeting CD22

    Natalia V. Giltiay1, Geraldine L. Shu2, Anthony Shock3 and Edward A. Clark1,2, 1Division of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, 2Department of Immunology, University of Washington, Seattle, WA, 3UCB Pharma, Slough, United Kingdom

    Background/Purpose: Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and production of autoantibodies. Treatment of patients with moderate-to-severe SLE with epratuzumab, a humanized…
  • Abstract Number: 1108 • 2015 ACR/ARHP Annual Meeting

    Epratuzumab, a Monoclonal Antibody Targeting CD22 on B Cells, Stimulates the Phosphorylation of Upstream Inhibitory Signals of the B Cell Receptor

    Simon Lumb1, Sarah J. Fleischer2, Capucine Daridon2, Alison Maloney1, Anthony Shock1 and Thomas Dorner2, 1UCB Pharma, Slough, United Kingdom, 2Charité University Medicine Berlin, CC12, Dept. Medicine/Rheumatology and Clinical Immunology and German Rheumatism Research Center Berlin (DRFZ), a Leibniz Institute, Berlin, Germany

    Background/Purpose: Epratuzumab, a humanized monoclonal antibody targeting CD22, is currently in phase 3 clinical trials in patients with systemic lupus erythematosus (SLE). Previous work suggests…
  • Abstract Number: 1109 • 2015 ACR/ARHP Annual Meeting

    Co-Crystal Structure of TACI and APRIL-BAFF-BAFF Heteromer Suggests That Charged Residues in APRIL and BAFF Dictate Their Receptor Binding Affinities

    Xuliang Jiang1, Thomas Tan2, Klaus Maskos3, Alfred Lammens3, Pascal Schneider4 and Wolf Palinksy5, 1Research and Development Institute, EMD Serono, Billerica, MA, 2EMD Serono Research, Billerica, MD, 3Proteros Biostructures GmbH, Planegg, Germany, 4Biochemistry, University of Lausanne, Epalinges, Switzerland, 5Global Biotech Development, Merck Serono, Aubonne, Switzerland

    Background/Purpose: The human B cell survival factor, B cell activation factor (BAFF), and its closely related homologue, a proliferation-inducing ligand (APRIL), modulate B cell functions…
  • Abstract Number: 1110 • 2015 ACR/ARHP Annual Meeting

    A Proliferative Inducing Ligand (APRIL) Promotes IL-10 Production of Human B Cells

    Charlotte Hua1, Rachel Audo2, Nataliya Yeremenko3, Dominique Baeten4, Michael Hahne2, Bernard Combe5, Jacques Morel5 and Claire I. Daien5, 1Department of Rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France, 2IGMM-CNRS UMR5535, Montpellier, France, 3Academic medical center, University of Amsterdam, Amsterdam, France, 41Academic Medical Center / University of Amsterdam, Amsterdam, Netherlands, 5Department of rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France

    Background/Purpose: B cells may have a negative regulatory role, mainly mediated by interleukin 10 (IL-10). We recently showed that regulatory B-cell functions are impaired in…
  • Abstract Number: 1111 • 2015 ACR/ARHP Annual Meeting

    Relapse of Lupus after B-Cell Depletion Therapy Is Associated with Loss of Apoptotic Cell Clearance and Elevated Type I Interferon Responses in Lupus Prone BXD2

    Hui-Chen Hsu1,2, Zhaoqi Yan3, PingAr Yang2, Qi Wu1,2, Jennie Hamilton4, Jun Li5, Hao Li6, Bao Luo6, Laurie Harrington3 and John Mountz7, 1Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 2Department of Medicine, Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 3Cell, Developmntl & Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, 4University of Alabama at Birmingham, Birmingham, AL, 5Medicine, University of Alabama at Birmingham, Birmingham, AL, 6Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 7Dept of Med/Rheumatology Div, University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, AL

    Background/Purpose: B-cell depletion therapy (BCDT) is a promising therapy for autoimmune diseases but relapse can occur.  In rheumatoid arthritis, patients who did not respond well…
  • Abstract Number: 1112 • 2015 ACR/ARHP Annual Meeting

    Obinutuzumab Outperforms Rituximab at Inducing B-Cell Cytotoxicity in Vitro through Fc-Mediated Effector Mechanisms in Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Venkat Reddy1, Christian Klein2, David A. Isenberg3, Geraldine Cambridge4, Martin Glennie5, Mark Cragg6 and Maria J. Leandro1, 1Rheumatology, University College London, London, United Kingdom, 2Roche Pharmaceutical Research & Early Development Oncology Discovery & Translational Area, Roche Glycart AG, Schlieren, Switzerland, 3Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom, 4Rheumatology, Centre for Rheumatology and Bloomsbury Rheumatology Unit, University College London, London, United Kingdom, 5Antibody and Vaccine group, Southampton University, Southampton, United Kingdom, 6Antibody and Vaccine group, Cancer Sciences Unit, Faculty of Medicine, Southampton University, Southampton, United Kingdom

    Background/Purpose: Obinutuzumab (OBZ, a Type II anti-CD20 monoclonal antibody [mAb] with afucosylated Fc portion and enhanced affinity for Fcγ receptor III) is more efficient than…
  • Abstract Number: 1113 • 2015 ACR/ARHP Annual Meeting

    B Cell Signature Profiling in Systemic Lupus Erythematosus Patients on Belimumab

    Michelle T. Ngo1, Abigail Benitez2, Kimberly J. Payne2, Michael De Vera3, Terry Ann Milford2 and Karina Marianne D. Torralba4, 1Rheumatology, Loma Linda University, Loma Linda, CA, 2Loma Linda University, Loma Linda, CA, 3Transplant Surgery, Loma Linda University, Loma Linda, CA, 4Division of Rheumatology, Department of Internal Medicine, Loma Linda University, Loma Linda, CA

    Background/Purpose:   The B cell pool is composed of subsets with different phenotypes and functions that mainly have effector functions to maintain immunologic tolerance. These…
  • Abstract Number: 1114 • 2015 ACR/ARHP Annual Meeting

    Profiling Circulating Plasmablasts from Anti-Ro Positive Mothers of Children with Congenital Heart Block to Identify Antigenic Targets Conferring Pathogenicity

    Sarah Kongpachith1, WH Robinson1, Sara Rasmussen2, Robert Clancy3 and Jill P. Buyon3, 1Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, 2Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, 3Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY

    Background/Purpose: Neonatal lupus (NL) is an uncommon autoimmune disease classically manifest as permanent complete heart block and/or transient cutaneous lesions. By definition of NL, there…
  • Abstract Number: 1115 • 2015 ACR/ARHP Annual Meeting

    B Cell-Intrinsic Interferon Gamma Signals Promote the Development of Systemic Lupus Erythematosus By Enhancing the Formation of Spontaneous Autoimmune Germinal Centers

    Shaun Jackson, Nicole Scharping, Holly Jacobs, Tanvi Arkatkar, Socheath Khim and David Rawlings, Seattle Children's Research Institute, Seattle, WA

    Background/Purpose: Type 1 interferon (IFN) is strongly implicated in lupus pathogenesis, and SLE patients frequently express a “type 1 IFN gene signature”. The type 2…
  • Abstract Number: 1116 • 2015 ACR/ARHP Annual Meeting

    Decreased Expression of Negative Regulators of Toll-like Receptor Signaling and Increased TLR7 Responsiveness in Expanded IgD- CD27- B Cells from Systemic Lupus Erythematosus Patients

    Scott Jenks1, Benjamin Barwick2 and Ignacio Sanz3, 1Allergy, Immunology, and Rheumatology, Emory University School of Medicine, Atlanta, GA, 2Emory University, Altanta, GA, 3Medicine, Emory University, Atlanta, GA

    Background/Purpose: B cell homeostasis is perturbed in SLE patients; in particular many patients with active disease have a large expansion of IgD- CD27- B cells…
  • Abstract Number: 1117 • 2015 ACR/ARHP Annual Meeting

    The B Cell Survival Cytokine BAFF Promotes Systemic Lupus Erythematosus Via Activation of TACI, Not BAFF Receptor

    Holly Jacobs1, Christopher Thouvenel1, Tanvi Arkatkar1, Nicole Scharping1, David Rawlings2 and Shaun Jackson1, 1Seattle Children's Research Institute, Seattle, WA, 2Pediatrics/Immunology, Washington, Seattle, WA

    Background/Purpose: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by polyclonal B cell activation and production of class-switched antinuclear antibodies (ANA). Transgenic mice…
  • Abstract Number: 1118 • 2015 ACR/ARHP Annual Meeting

    Role of the Chemokine Receptor CXCR3 in the Function of Regulatory B Cells in Patients with SLE

    Shun-ichiro Ota1,2, Hiroaki Niiro3, Naoko Ueki2,4, Yuri Hirosaki2, Hirofumi Tsuzuki2, Siamak Jabbarzadeh-Tabrizi2, Tsuyoshi Nakayama2, Koji Mishima2, Ayako Takaki2, Hiroki Mitoma2, Mitsuteru Akahoshi2, Yojiro Arinobu2, Hiroshi Tsukamoto2 and Koichi Akashi2, 1Department of Rheumatology, Internal medicine and connective tissue disorders, Shimonoseki City Hospital, Shimonoseki, Japan, 2Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan, 3Clinical Education Center, Kyushu University Hospital, Fukuoka, Japan, 4Division of Nephrology and Rheumatology, Fukuoka University, Fukuoka, Japan

    Background/Purpose: The emerging application of B-cell directed therapies in autoimmune diseases has led to the discovery of a novel B cell population, referred to as…
  • Abstract Number: 1119 • 2015 ACR/ARHP Annual Meeting

    High Resolution Motif Mapping of in Situ Anti-Native-Vimentin Antibodies in Lupus Tubulointerstitial Nephritis

    Andrew Kinloch1, Yuta Asano2, Balazs Banfai3, Gregor Dernick3, Carole Henry Dunand4, Nirit Mor-Vaknin5, Maureen Legendre5, David Markovitz5, Thomas Schindler6 and Marcus R. Clark7, 1University of Chicago, Chicago, IL, 2Committee of immunology, University of Chicago, Chicago, IL, 3Translational Technologies and Bioinformatics, Roche, Basel, Switzerland, 4Rheumatology and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, 5University of Michigan, Ann Arbor, MI, 6Roche Innovation Center Basel, Roche, Basel, Switzerland, 7Rheumatology 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 an in situ autoantibody response. By characterizing monoclonal antibodies engineered from…
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