title: Protective autoantibodies in the rheumatic diseases: lessons for therapy.
abstract: The adaptive immune system augments host defenses against diverse infectious threats, yet also carries intertwined risks for the development of autoimmune disease. The immune system incorporates homeostatic pathways for essential housekeeping functions that involve recognition of oxidation-modified endogenous molecules. Now, the properties of a physiological class of natural autoantibodies, which seem to modulate the severity or even prevent the onset of autoimmune disease, are beginning to be defined. Whereas disease-associated IgG autoantibodies to nuclear antigens and citrulline-modified self-proteins have been shown to activate innate pattern recognition receptors leading to increased cell death and tissue injury, a class of IgM autoantibodies to oxidation-associated neo-antigens can oppose these pathogenic effects. These naturally arising regulatory IgM autoantibodies enhance the capacity for the phagocytic clearance of host cells affected by programmed death pathways. These antibodies can also suppress key signalling pathways in the innate immune system involved in the control and resolution of inflammatory responses to Toll-like receptor agonists and disease-associated IgG autoantibodies.
authors.affiliation: Laboratory of B-Cell Immunobiology, Departments of Medicine and Pathology, NYU School of Medicine, Alexandria Center, Room 804, 450 East 29th Street, New York, NY 10016, USA. gregg.silverman@ nyumc.org
authors.forename: Gregg J
authors.initials: GJ
authors.lastname: Silverman
authors.forename: Jaya
authors.initials: J
authors.lastname: Vas
authors.forename: Caroline
authors.initials: C
authors.lastname: Grönwall
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D056747:Immunomodulation; D012216:Rheumatic Diseases / Q000276:immunology* / Q000378:metabolism / Q000628:therapy
chemical_list: D001323:Autoantibodies; D007075:Immunoglobulin M