Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by 'autoantigen complementarity'
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Authors
Reynolds, JohnPreston, Gloria A.
Pressler, Barrak M.
Hewins, Peter
Brown, Michael
Roth, Aleeza
Alderman, Elizabeth
Bunch, Donna
Jennette, J. Charles
Cook, H. Terence
Falk, Ronald J.
Pusey, Charles D.
Affiliation
Imperial College LondonUniversity of North Carolina at Chapel Hill
University of Bedfordshire
Issue Date
2015-04-02Subjects
immunology
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'Autoantigen complementarity' is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is 'antisense/complementary' to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that 'complement' the well characterized epitope on α3(IV)NC1, pCol(24-38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24-38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24-38) sequence. Interestingly, anti-complementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for 'autoantigen complementarity' in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected 'complementary' antigens.Citation
Reynolds J, Preston GA, Pressler BM, Hewins P, Brown M, Roth A, Alderman E, Bunch D, Jennette JC, Cook HT, Falk RJ, Pusey CD (2015) 'Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by 'autoantigen complementarity'', Journal of Autoimmunity, 59 (), pp.8-18.Publisher
ElsevierJournal
Journal of AutoimmunityPubMed ID
25841937PubMed Central ID
PMC4459745Additional Links
https://www.sciencedirect.com/science/article/pii/S0896841115000049https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459745/
Type
ArticleLanguage
enISSN
0896-8411EISSN
0896-8411ae974a485f413a2113503eed53cd6c53
10.1016/j.jaut.2015.01.003
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