Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (...

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Main Authors: Robert Root-Bernstein, Jacob Couturier
Format: Article
Language:English
Published: Wiley 2006-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1080/17402520600578731
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author Robert Root-Bernstein
Jacob Couturier
author_facet Robert Root-Bernstein
Jacob Couturier
author_sort Robert Root-Bernstein
collection DOAJ
description We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.
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spelling doaj-art-3c09c1a4022f456c86fa79be5f65f5db2025-02-03T01:22:15ZengWileyClinical and Developmental Immunology1740-25221740-25302006-01-01131496510.1080/17402520600578731Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia PurpuraRobert Root-Bernstein0Jacob Couturier1Department of Physiology, Michigan State University, East Lansing, MI, USADepartment of Physiology, Michigan State University, East Lansing, MI, USAWe describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.http://dx.doi.org/10.1080/17402520600578731
spellingShingle Robert Root-Bernstein
Jacob Couturier
Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura
Clinical and Developmental Immunology
title Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura
title_full Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura
title_fullStr Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura
title_full_unstemmed Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura
title_short Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura
title_sort antigenic complementarity in the origins of autoimmunity a general theory illustrated with a case study of idiopathic thrombocytopenia purpura
url http://dx.doi.org/10.1080/17402520600578731
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