RESEARCH - A general theory of the origins of autoimmunity illustrated with a case study of ITP

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Clin Dev Immunol. 2006 Mar;13(1):49-65.

Antigenic complementarity in the origins of autoimmunity: A general theory

illustrated with a case study of idiopathic thrombocytopenia purpura.

Root-Bernstein R, Couturier J.

Michigan State University, Department of Physiology, East Lansing, MI, USA.

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.

PMID: 16603444

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16603444

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Mayo Clinic in Rochester

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s Hopkins Medicine

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