Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases

Annual Review of Immunology
Antony Rosen, Livia Casciola-Rosen

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.

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Citations

Jul 9, 2016·Arthritis Research & Therapy·Joanna E ParkesUNKNOWN Myositis Genetics Consortium (MYOGEN)
Sep 30, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hanna KimRaphaela Goldbach-Mansky
Apr 7, 2017·Arthritis & Rheumatology·Jean-Luc SenécalYves Troyanov
Feb 2, 2017·Annual Review of Immunology·John T CrowlDaniel B Stetson
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Sep 19, 2019·Immunological Medicine·Takeshi Tsubata
Aug 10, 2019·Frontiers in Immunology·Jenna McGowanRitu Chakravarti
Apr 8, 2020·Journal of Immunology Research·Bin WangGuixiu Shi
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Aug 8, 2021·International Journal of Molecular Sciences·Nadezhda TodorovaIvanka Tsacheva

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Methods Mentioned

BETA
immunoprecipitation
ELISA
acetylation

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