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Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases

Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases Systemic autoimmune diseases are characterized by specific targeting of a limited group of ubiquitously expressed autoantigens by the immune system. This review examines the mechanisms underlying their selection as immune targets. Initiation of autoimmune responses likely reflects the presentation of antigens with a distinct structure not previously encountered by the immune system, in a proimmune context (injury, malignancy, or infection). Causes of modified structure include somatic mutation and posttranslational modifications (including citrullination and proteolysis). Many autoantigens are components of multimolecular complexes, and some of the other components may provide adjuvant activity. Propagation of autoimmune responses appears to reflect a bidirectional interaction between the immune response and the target tissues in a mutually reinforcing cycle: Immune effector pathways generate additional autoantigen, which feeds further immune response. We propose that this resonance may be a critical principle underlying disease propagation, with specific autoantigens functioning as the hubs around which amplification occurs. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Immunology Annual Reviews

Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases

Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases


Systemic autoimmune diseases are characterized by specific targeting of a limited group of ubiquitously expressed autoantigens by the immune system. This review examines the mechanisms underlying their selection as immune targets. Initiation of autoimmune responses likely reflects the presentation of antigens with a distinct structure not previously encountered by the immune system, in a proimmune context (injury, malignancy, or infection). Causes of modified structure include somatic mutation and posttranslational modifications (including citrullination and proteolysis). Many autoantigens are components of multimolecular complexes, and some of the other components may provide adjuvant activity. Propagation of autoimmune responses appears to reflect a bidirectional interaction between the immune response and the target tissues in a mutually reinforcing cycle: Immune effector pathways generate additional autoantigen, which feeds further immune response. We propose that this resonance may be a critical principle underlying disease propagation, with specific autoantigens functioning as the hubs around which amplification occurs. INTRODUCTION: A CONCEPTUAL FRAMEWORK Induction of an immune response against self-antigens, which damages self-tissues, is a central feature of autoimmune diseases. Over the last 50 years, there has been significant progress in defining the molecules that are targeted in autoimmune diseases, largely using high-titer autoantibodies as probes (1). The resulting catalog of autoantigens, together with careful clinical descriptions of the distinct disease features associated with such responses, has provided a critical framework to begin to understand the mechanisms responsible for antigen selection in autoimmune diseases (2). It is noteworthy that the antigenic targets of the highly driven immune responses in...
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Publisher
Annual Reviews
Copyright
Copyright © 2016 by Annual Reviews. All rights reserved
ISSN
0732-0582
eISSN
1545-3278
DOI
10.1146/annurev-immunol-032414-112205
pmid
26907212
Publisher site
See Article on Publisher Site

Abstract

Systemic autoimmune diseases are characterized by specific targeting of a limited group of ubiquitously expressed autoantigens by the immune system. This review examines the mechanisms underlying their selection as immune targets. Initiation of autoimmune responses likely reflects the presentation of antigens with a distinct structure not previously encountered by the immune system, in a proimmune context (injury, malignancy, or infection). Causes of modified structure include somatic mutation and posttranslational modifications (including citrullination and proteolysis). Many autoantigens are components of multimolecular complexes, and some of the other components may provide adjuvant activity. Propagation of autoimmune responses appears to reflect a bidirectional interaction between the immune response and the target tissues in a mutually reinforcing cycle: Immune effector pathways generate additional autoantigen, which feeds further immune response. We propose that this resonance may be a critical principle underlying disease propagation, with specific autoantigens functioning as the hubs around which amplification occurs.

Journal

Annual Review of ImmunologyAnnual Reviews

Published: May 20, 2016

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