Systemic lupus erythematosus and related autoimmune diseases are antigen-driven, epigenetic diseases

Autoimmune diseases result when cellular stresses (ex UV, cell cycle, hormones, viruses, and/or drugs) induce altered expression of polyamines, leading to chromatin disruption, interference with chromatin methylation, exposure of sequestered genes, and interference with tissue-specific processes. Ex...

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Bibliographic Details
Published in:Medical hypotheses 2002-12, Vol.59 (6), p.736-741
Main Author: Brooks, Wesley H
Format: Article
Language:English
Subjects:
Autoantigens - immunology
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
DNA Methylation
Humans
Lupus Erythematosus, Systemic - genetics
Lupus Erythematosus, Systemic - immunology
Models, Genetic
Polyamines - metabolism
RNA-Directed DNA Polymerase - metabolism
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Summary:Autoimmune diseases result when cellular stresses (ex UV, cell cycle, hormones, viruses, and/or drugs) induce altered expression of polyamines, leading to chromatin disruption, interference with chromatin methylation, exposure of sequestered genes, and interference with tissue-specific processes. Exposure of previously sequestered Alu and LINE-1 sequences can lead to reverse transcription of Alu-RNA (and other transcripts) by the LINE-1 reverse transcriptase, yielding autoantigenic, hypomethylated DNA fragments. Release from the cell of the hypomethylated DNA fragments, along with polyamine-associated nucleoprotein complexes formed with the fragments, would elicit the autoimmune response. Loss of gene control due to hypomethylation and chromatin disruption by polyamines or other factors can include loss of dosage compensation from the inactive X chromosome for spermine synthase and spermidine/spermine N 1-acetyltransferase at Xp22.1. This leads to ongoing altered polyamine levels. Thus, autoimmune diseases result from epigenetic changes that lead to autoantigen generation.
ISSN:0306-9877
1532-2777
DOI:10.1016/S0306-9877(02)00322-5