The Complement System in Renal Diseases
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
B Cell Checkpoints in Autoimmune Rheumatic Diseases
REVIEWS B cell checkpoints in autoimmune rheumatic diseases Samuel J. S. Rubin1,2,3, Michelle S. Bloom1,2,3 and William H. Robinson1,2,3* Abstract | B cells have important functions in the pathogenesis of autoimmune diseases, including autoimmune rheumatic diseases. In addition to producing autoantibodies, B cells contribute to autoimmunity by serving as professional antigen- presenting cells (APCs), producing cytokines, and through additional mechanisms. B cell activation and effector functions are regulated by immune checkpoints, including both activating and inhibitory checkpoint receptors that contribute to the regulation of B cell tolerance, activation, antigen presentation, T cell help, class switching, antibody production and cytokine production. The various activating checkpoint receptors include B cell activating receptors that engage with cognate receptors on T cells or other cells, as well as Toll-like receptors that can provide dual stimulation to B cells via co- engagement with the B cell receptor. Furthermore, various inhibitory checkpoint receptors, including B cell inhibitory receptors, have important functions in regulating B cell development, activation and effector functions. Therapeutically targeting B cell checkpoints represents a promising strategy for the treatment of a variety of autoimmune rheumatic diseases. Antibody- dependent B cells are multifunctional lymphocytes that contribute that serve as precursors to and thereby give rise to acti- cell- mediated cytotoxicity to the pathogenesis of autoimmune diseases -
The Case for Lupus Nephritis
Journal of Clinical Medicine Review Expanding the Role of Complement Therapies: The Case for Lupus Nephritis Nicholas L. Li * , Daniel J. Birmingham and Brad H. Rovin Department of Internal Medicine, Division of Nephrology, The Ohio State University, Columbus, OH 43210, USA; [email protected] (D.J.B.); [email protected] (B.H.R.) * Correspondence: [email protected]; Tel.: +1-614-293-4997; Fax: +1-614-293-3073 Abstract: The complement system is an innate immune surveillance network that provides defense against microorganisms and clearance of immune complexes and cellular debris and bridges innate and adaptive immunity. In the context of autoimmune disease, activation and dysregulation of complement can lead to uncontrolled inflammation and organ damage, especially to the kidney. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance, autoantibody production, and immune complex deposition in tissues including the kidney, with inflammatory consequences. Effective clearance of immune complexes and cellular waste by early complement components protects against the development of lupus nephritis, while uncontrolled activation of complement, especially the alternative pathway, promotes kidney damage in SLE. Therefore, complement plays a dual role in the pathogenesis of lupus nephritis. Improved understanding of the contribution of the various complement pathways to the development of kidney disease in SLE has created an opportunity to target the complement system with novel therapies to improve outcomes in lupus nephritis. In this review, we explore the interactions between complement and the kidney in SLE and their implications for the treatment of lupus nephritis. Keywords: lupus nephritis; complement; systemic lupus erythematosus; glomerulonephritis Citation: Li, N.L.; Birmingham, D.J.; Rovin, B.H. -
Chapter 1 Chapter 1
Chapter 1 General introduction Chapter 1 1.1 Overview of the complement system 1.2 Complement activation pathways 1.2.1 The lectin pathway of complement activation 1.2.2 The alternative pathway of complement activation 1.2.3 The classical pathway of complement activation 1.2.4 The terminal complement pathway 1.3 Regulators and modulators of the complement system 1.4 The evolution of the complement system 1.4.1 Findings in nature 1.4.2 Protein families 1.5 The ancient complement system 1.6 Can complement deficiencies clarify complement function? 1.7 Introduction to this thesis 10 INTRODUCTION: THE COMPLEMENT SYSTESYSTEMM IN HISTORICAL PERSPERSPECTIVEPECTIVE Abbreviations AP : alternative complement pathway C1-INH : C1 esterase inhibitor CP : classical complement pathway CR1 : complement receptor 1 (CD35) CRP : C-reactive protein DAF : decay-accelerating factor (CD55) Ig : immunoglobulin LP : lectin complement pathway MBL : mannose-binding lectin MCP : membrane cofactor protein (CD46) MHC : major histocompatibility complex RCA : regulators of complement activation SLE : systemic lupus erythomatosus Classification of species or phyla in evolution Agnatha : jawless vertebrates like hagfish and lamprey Ascidian: : belongs to the subphylum urochordata Chordata: : phylum comprising urochordata, cephalochordata and vertebrata Cyclostome : e.g. lamprey Deuterostome : comprises two major phyla, the chordata (including mammals) and the echinodermata Echinodermata : (ekhinos = sea urchin, derma = skin) phylum including sea urchins, sea stars, and seacucumbers Invertebrates : echinoderms, and protochordates like Clavelina picta and the ascidian Halocynthia roretzi Teleost fish : bony fish like trout, sand bass, and puffer fish Tunicate : belongs to the phylum of the urochordata Urochordata : subphylum Vertebrates : classified in jawless (Agnatha) or jawed species THE COMPLEMENT SYSTESYSTEMM 1.1 Overview of the complement system (Fig.(Fig. -
Autoantibody Development Under Treatment with Immune-Checkpoint Inhibitors Emma C
Published OnlineFirst November 13, 2018; DOI: 10.1158/2326-6066.CIR-18-0245 Cancer Immunology Miniature Cancer Immunology Research Autoantibody Development under Treatment with Immune-Checkpoint Inhibitors Emma C. de Moel1, Elisa A. Rozeman2, Ellen H. Kapiteijn3, Els M.E. Verdegaal3, Annette Grummels4,JaapA.Bakker4, Tom W.J. Huizinga1, John B. Haanen2,3, Rene E.M. Toes1, and Diane van der Woude1 Abstract Immune-checkpoint inhibitors (ICIs) activate the and any irAEs [OR, 2.92; 95% confidence interval (CI) immune system to assault cancer cells in a manner that is 0.85–10.01]. Patients with antithyroid antibodies after ipi- not antigen specific. We hypothesized that tolerance may limumab had significantly more thyroid dysfunction under also be broken to autoantigens, resulting in autoantibody subsequent anti–PD-1 therapy: 7/11 (54.6%) patients with formation, which could be associated with immune-related antithyroid antibodies after ipilimumab developed thyroid adverse events (irAEs) and antitumor efficacy. Twenty-three dysfunction under anti–PD1 versus 7/49 (14.3%) patients common clinical autoantibodies in pre- and posttreatment without antibodies (OR, 9.96; 95% CI, 1.94–51.1). Patients sera from 133 ipilimumab-treated melanoma patients were who developed autoantibodies showed a trend for better determined, and their development linked to the occurrence survival (HR for all-cause death: 0.66; 95% CI, 0.34–1.26) of irAEs, best overall response, and survival. Autoantibodies and therapy response (OR, 2.64; 95% CI, 0.85–8.16). We developed in 19.2% (19/99) of patients who were autoan- conclude that autoantibodies develop under ipilimumab tibody-negative pretreatment. -
Ability of CR1-Deficient Erythrocytes This Information Is Current As of October 3, 2021
A Soluble Recombinant Multimeric Anti-Rh(D) Single-Chain Fv/CR1 Molecule Restores the Immune Complex Binding Ability of CR1-Deficient Erythrocytes This information is current as of October 3, 2021. S. Oudin, M. Tonye Libyh, D. Goossens, X. Dervillez, F. Philbert, B. Réveil, F. Bougy, T. Tabary, P. Rouger, D. Klatzmann and J. H. M. Cohen J Immunol 2000; 164:1505-1513; ; doi: 10.4049/jimmunol.164.3.1505 Downloaded from http://www.jimmunol.org/content/164/3/1505 References This article cites 54 articles, 25 of which you can access for free at: http://www.jimmunol.org/content/164/3/1505.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 3, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. A Soluble Recombinant Multimeric Anti-Rh(D) Single-Chain Fv/CR1 Molecule Restores the Immune Complex Binding Ability of CR1-Deficient Erythrocytes S. -
Tests for Autoimmune Diseases Test Codes 249, 16814, 19946
Tests for Autoimmune Diseases Test Codes 249, 16814, 19946 Frequently Asked Questions Panel components may be ordered separately. Please see the Quest Diagnostics Test Center for ordering information. 1. Q: What are autoimmune diseases? A: “Autoimmune disease” refers to a diverse group of disorders that involve almost every one of the body’s organs and systems. It encompasses diseases of the nervous, gastrointestinal, and endocrine systems, as well as skin and other connective tissues, eyes, blood, and blood vessels. In all of these autoimmune diseases, the underlying problem is “autoimmunity”—the body’s immune system becomes misdirected and attacks the very organs it was designed to protect. 2. Q: Why are autoimmune diseases challenging to diagnose? A: Diagnosis is challenging for several reasons: 1. Patients initially present with nonspecific symptoms such as fatigue, joint and muscle pain, fever, and/or weight change. 2. Symptoms often flare and remit. 3. Patients frequently have more than 1 autoimmune disease. According to a survey by the Autoimmune Diseases Association, it takes up to 4.6 years and nearly 5 doctors for a patient to receive a proper autoimmune disease diagnosis.1 3. Q: How common are autoimmune diseases? A: At least 30 million Americans suffer from 1 or more of the 80 plus autoimmune diseases. On average, autoimmune diseases strike three times more women than men. Certain ones have an even higher female:male ratio. Autoimmune diseases are one of the top 10 leading causes of death among women age 65 and under2 and represent the fourth-largest cause of disability among women in the United States.3 Women’s enhanced immune system increases resistance to infection, but also puts them at greater risk of developing autoimmune disease than men. -
Understanding the Immune System: How It Works
Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them. -
Systemic Lupus Erythematosus T Cell Studies in a Peptide-Induced Model Of
T Cell Studies in a Peptide-Induced Model of Systemic Lupus Erythematosus Magi Khalil, Kayo Inaba, Ralph Steinman, Jeffrey Ravetch and Betty Diamond This information is current as of September 25, 2021. J Immunol 2001; 166:1667-1674; ; doi: 10.4049/jimmunol.166.3.1667 http://www.jimmunol.org/content/166/3/1667 Downloaded from References This article cites 73 articles, 40 of which you can access for free at: http://www.jimmunol.org/content/166/3/1667.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 25, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. T Cell Studies in a Peptide-Induced Model of Systemic Lupus Erythematosus Magi Khalil,* Kayo Inaba,‡ Ralph Steinman,‡ Jeffrey Ravetch,‡ and Betty Diamond1† We have previously reported that immunization with a peptide mimetope of dsDNA on a branched polylysine backbone (DWEYSVWLSN-MAP) induces a systemic lupus erythematosus-like syndrome in the nonautoimmune BALB/c mouse strain. -
Isolation and Characterization of Complement Receptor Type 1 from Rat Glomerular Epithelial Cells
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 43 (1993), pp. 730—736 RAPID COMMUNICATION Isolation and characterization of complement receptor type 1 from rat glomerular epithelial cells RICHARD J. QUIGG, MITCHEL L. GALISHOFF, ARTHUR B. SNEED, III, and DAVID KIM Division of Nephrology, Department of Internal Medicine, Medical College of Virginia, Richmond, Virginia, USA Isolation and characterization of complement receptor type 1 from rat studies using rosetting or immunostaining techniques that have glomerular epithelial cells. Complement receptor type 1 (C3b/C4b re- shown alterations in CR! in human renal disease [6, 11—17]. ceptor, CR1) is known to be present in human glomerular epithelial cells (GEC) in vivo. The presence of CR1 has not been documented in rat From these studies, it appears that the expression of CR1 glomeruli, although cultured rat GEC appear to express CR1 basedprotein is diminished in proliferative glomerular diseases, but a upon their ability to rosette with complement-coated erythrocytes. In consistent pattern among other disease types has not yet this study, we establish that CR1 is present in cultured rat GEC: (1) by emerged. isolating a 200 kDa protein from detergent-solubilized cultured rat GEC In this study, we isolated a protein of 200 kDa by subjecting through the use of C3b affinity chromatography; (2) by Western blotting studies demonstrating reactivity of anti-human CR1 antibodies with this detergent-solubiized cultured rat GEC to C3b affinity chroma- protein from cultured GEC; and (3) by demonstrating that C3b binding tography. -
Complement Receptor 1 Therapeutics for Prevention of Immune Hemolysis
Review: complement receptor 1 therapeutics for prevention of immune hemolysis K.YAZDANBAKHSH The complement system plays a crucial role in fighting infections biological activities, it has to be activated. Activation and is an important link between the innate and adaptive immune occurs in a sequence that involves proteolytic cleavage responses. However, inappropriate complement activation can cause tissue damage, and it underlies the pathology of many of the complement components, resulting in the diseases. In the transfusion medicine setting, complement release of active biological mediators and the assembly sensitization of RBCs can lead to both intravascular and of active enzyme molecules that result in cleavage of extravascular destruction. Moreover, complement deficiencies are 1 associated with autoimmune disorders, including autoimmune the next downstream complement component. hemolytic anemia (AIHA). Complement receptor 1 (CR1) is a large Depending on the nature of the activators, three single-pass glycoprotein that is expressed on a variety of cell types complement activation pathways have been described: in blood, including RBCs and immune cells. Among its multiple the antibody-dependent classical pathway and the functions is its ability to inhibit complement activation. Furthermore, gene knockout studies in mice implicate a role for antibody-independent alternative and lectin pathways CR1 (along with the alternatively spliced gene product CR2) in (Fig. 1).1 Common to all three pathways are two prevention of autoimmunity. This review discusses the possibility critical steps: the assembly of the C3 convertase that the CR1 protein may be manipulated to prevent and treat AIHA. In addition, it will be shown in an in vivo mouse model of enzymes and the activation of C5 convertases. -
C1q and Mannose-Binding Lectin Interact with CR1 in The
C1q and Mannose-Binding Lectin Interact with CR1 in the Same Region on CCP24-25 Modules Mickaël Jacquet, Gianluca Cioci, Guillaume Fouet, Isabelle Bally, Nicole Thielens, Christine Gaboriaud, Véronique Rossi To cite this version: Mickaël Jacquet, Gianluca Cioci, Guillaume Fouet, Isabelle Bally, Nicole Thielens, et al.. C1q and Mannose-Binding Lectin Interact with CR1 in the Same Region on CCP24-25 Modules. Frontiers in Immunology, Frontiers, 2018, 9 (453), 11 p. 10.3389/fimmu.2018.00453. hal-01730166 HAL Id: hal-01730166 https://hal.univ-grenoble-alpes.fr/hal-01730166 Submitted on 5 Dec 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License ORIGINAL RESEARCH published: 07 March 2018 doi: 10.3389/fimmu.2018.00453 C1q and Mannose-Binding Lectin Interact with CR1 in the Same Region on CCP24-25 Modules Mickaël Jacquet, Gianluca Cioci, Guillaume Fouet, Isabelle Bally, Nicole M. Thielens, Christine Gaboriaud and Véronique Rossi* Univ. Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France Complement receptor type 1 (CR1) is a multi modular membrane receptor composed of 30 homologous complement control protein modules (CCP) organized in four different functional regions called long homologous repeats (LHR A, B, C, and D). -
Alternative Pathway of Complement: Demonstration and Characterization of Initiating Factor and Its Properdin-Independent Function*' $
ALTERNATIVE PATHWAY OF COMPLEMENT: DEMONSTRATION AND CHARACTERIZATION OF INITIATING FACTOR AND ITS PROPERDIN-INDEPENDENT FUNCTION*' $ BY ROBERT D. SCHREIBER,§ OTTO GOTZE,II AND HANS J. MTJLLER-EBERHARD¶ (From the Department of Molecular Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037) In 1954 Pillemer and associates (2) introduced the properdin system as a humoral mechanism of natural resistance to infections. Although this provoca- tive hypothesis generated a large body of literature, it could not be critically evaluated until recently. The past 5 yr of complement research brought to light an unanticipated complexity of the properdin system. The design of a rational model of the properdin pathway had to await identification of the major compo- nents and insight into their interactions. In this communication and subsequent papers (3 and footnote 1), we wish to report the results of experiments that together with previously published obser- vations have allowed the formulation of a comprehensive molecular concept of the properdin pathway (4). The dynamics of the pathway involve the recruit- ment of the initiating factor (IF), 2 sequential formation of C3 and C5 conver- tases, activation of properdin, and stabilization of the enzymes by activated properdin. The biological consequences of this process are identical to those resulting from activation of the classical pathway: generation of the anaphyla- toxins, immune adherence reactivity, opsonic activity, and formation of the membrane attack complex. The purpose of this paper is to describe (a) the initiating factor as a novel serum protein, (b) its function in the assembly of the initial C3 convertase of the * This is publication number 1158.