Nature and functions of autoantibodies
- 1 September 2008
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Clinical Practice Rheumatology
- Vol. 4 (9), 491-498
- https://doi.org/10.1038/ncprheum0895
Abstract
Although autoantibodies occur in healthy individuals, pathogenic autoantibodies are the key etiologic agent in many autoimmune diseases in humans, most notably lupus erythematosus. In this Review the authors explore how these autoantibodies become pathogenic, what accounts for their specificity, how they cause disease and whether they have a clinical role as biomarkers of disease. Antibodies that react with self-molecules occur in healthy individuals and are referred to as natural antibodies or autoantibodies. Natural autoantibodies are mainly IgM, are encoded by unmutated V(D)J genes and display a moderate affinity for self-antigens. They provide a first line of defense against infections, probably serve housekeeping functions and contribute to the homeostasis of the immune system. By contrast, high-affinity, somatically mutated IgG autoantibodies reflect a pathologic process whereby homeostatic pathways related to cell clearance, antigen-receptor signaling or cell effector functions are disturbed. In some autoimmune disorders, autoantibodies might be present before disease onset, show remarkable specificity and serve as biomarkers providing an opportunity for diagnosis and therapeutic intervention. In organ-specific autoimmune diseases, such as myasthenia gravis or pemphigus, autoantibodies directly bind to and injure target organs. In systemic autoimmune diseases, autoantibodies react with free molecules, such as phospholipids, as well as cell surface and nucleoprotein antigens, forming pathogenic antigen–antibody (immune) complexes. These autoantibodies injure tissues and organs through engagement of FcγR activation of complement as well as internalization and activation of Toll-like receptors. Activation of intracellular Toll-like receptors in plasmacytoid dendritic cells leads to the production of type I interferon, whereas engagement of intracellular Toll-like receptors on antigen-presenting cells stimulates cell activation and the production of other inflammatory cytokines. Thus, immune complexes might perpetuate a positive feedback loop amplifying inflammatory responses.Keywords
This publication has 61 references indexed in Scilit:
- Innate and adaptive immune response to apoptotic cellsJournal of Autoimmunity, 2007
- Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal diseaseClinical and Experimental Immunology, 2007
- Crystal Structure of a Human Autoimmune Complex between IgM Rheumatoid Factor RF61 and IgG1 Fc Reveals a Novel Epitope and Evidence for Affinity MaturationJournal of Molecular Biology, 2007
- The Broad Antibacterial Activity of the Natural Antibody Repertoire Is Due to Polyreactive AntibodiesCell Host & Microbe, 2007
- Natural antibody mediated innate autoimmune responseMolecular Immunology, 2007
- DNA repair in antibody somatic hypermutationTrends in Immunology, 2006
- The role of IgM antibodies in the recognition and clearance of apoptotic cellsMolecular Immunology, 2005
- Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c miceArthritis & Rheumatism, 1998
- Molecular Mimicry by Herpes Simplex Virus-Type 1: Autoimmune Disease After Viral InfectionScience, 1998
- CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoireImmunology Today, 1989