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2015 ; 59
(ä): 8-18
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Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is
triggered by autoantigen complementarity
#MMPMID25841937
Reynolds J
; Preston GA
; Pressler BM
; Hewins P
; Brown M
; Roth A
; Alderman E
; Bunch D
; Jennette JC
; Cook HT
; Falk RJ
; Pusey CD
J Autoimmun
2015[May]; 59
(ä): 8-18
PMID25841937
show ga
'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 ?3 chain of
type IV collagen. In this study, WKY rats were immunized with a complementary ?3
peptide (c-?3-Gly) comprised of amino acids that 'complement' the well
characterized epitope on ?3(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-?3-Gly-immunized
animals were shown to be specific for ?3 protein, binding in a region containing
sense pCol(24-38) sequence. Interestingly, anti-complementary ?3 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.