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- Title
Autoantigen complementarity: a new theory implicating complementary proteins as initiators of autoimmune disease.
- Authors
Pendergraft, William F.; Pressler, Barrak M.; Charles Jennette, J.; Falk, Ronald J.; Preston, Gloria A.
- Abstract
Autoimmune diseases affect approximately 1 in 21 persons in the United States. Treatment often requires long-term cytotoxic therapy. How and why these deleterious diseases occur is unclear. A serendipitous finding in our laboratory using serum from patients with autoimmune vasculitis led us to develop the theory of autoantigen complementarity, a novel concept that may elucidate the etiological and pathogenetic mechanisms underlying autoimmune disease in general. The theory proposes that the inciting immunogen that elicits a cascade of immunological events isnotthe self-antigen (the autoantigen) or its mimic but rather a protein that iscomplementaryin surface structure to the autoantigen; that is, a protein homologous or identical to the amino acid sequence of translated antisense RNA from the noncoding strand of the autoantigen gene. The cascade begins when this complementary protein initiates the production of antibodies that in turn elicit an anti-antibody or anti-idiotypic response. These anti-idiotypic antibodies can now react with the autoantigen. Strikingly, homology search of complementary proteins yields microbial and fungal proteins, thus indicating that invading micro-organisms can deliver the inciting immunogen. Curiously, approximately 50% of our patients transcribe the complementary protein’s antisense RNA. If it transpires that these aberrant RNAs are translated, the complementary protein would be produced by the individual. Here we review published research investigating complementary proteins, anti-idiotypic immune responses, and antisense transcripts, all of which support complementary proteins as initiators of autoimmune disease. In addition, we provide possible microbial and/or fungal organisms that may incite some of the most studied autoimmune diseases. Lastly, we propose mechanisms by which cell-mediated autoimmunity can be triggered by autoantigen complementarity. Based on our data and the contributions of the researchers described in this review, identification of proteins complementary to autoantigens is likely to be informative in most autoimmune diseases. This vein of study is in the early phases; however, we expect “autoantigen complementarity” is an underlying mechanism in many autoimmune diseases.
- Subjects
UNITED States; AUTOIMMUNE diseases; ANTINEOPLASTIC antibiotics; ANTINEOPLASTIC agents; AUTOIMMUNITY; IMMUNOLOGIC diseases
- Publication
Journal of Molecular Medicine, 2005, Vol 83, Issue 1, p12
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-004-0615-3