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The Role of Pathogenic Autoantibodies in Autoimmunity

Department of Molecular Biology and Medicine, Monash University, Clayton 3168, Australia
Author to whom correspondence should be addressed.
Academic Editor: Christiane Hampe
Antibodies 2015, 4(4), 314-353;
Received: 27 August 2015 / Revised: 26 October 2015 / Accepted: 3 November 2015 / Published: 10 November 2015
(This article belongs to the Special Issue Auto-Antibody and Autoimmune Disease)
The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID). Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb) show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig) class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them. View Full-Text
Keywords: autoimmune disease; monoclonal antibody; immunoglobulin; epitopes; Fc receptors; intracellular antigens; autoantibodies autoimmune disease; monoclonal antibody; immunoglobulin; epitopes; Fc receptors; intracellular antigens; autoantibodies
MDPI and ACS Style

Rowley, M.J.; Whittingham, S.F. The Role of Pathogenic Autoantibodies in Autoimmunity. Antibodies 2015, 4, 314-353.

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