Nephrology Dialysis Transplantation, Vol 13, Issue 3 602-607, Copyright © 1998 by Oxford University Press
J Ryan, I Katbamna, P Mason, C Pusey and A Turner
Background: Autoimmunity to the NC1 domain of the
&agr;3 chain of type IV collagen (&agr;3(IV)NC1), the Goodpasture
antigen, is the cause of spontaneous human antiglomerular basement membrane
(anti-GBM) disease, and of anti-GBM nephritis in several animal models.
Methods: We have derived amino acid sequences from
&agr;3(IV)NC1 for a number of mammalian species (monkey, sheep, pig,
dog, rabbit, and rat) by RT-PCR and cDNA cloning. The GBM of some species
was studied comparatively for binding to Goodpasture autoantibodies.
Results: From this work and other data the sequences
of nine mammalian species can be aligned. Regions and residues that may be
functionally important are identified. &agr;3(IV)NC1 sequences were
found to be less closely conserved across species than &agr;1 and
&agr;2(IV)NC1, 91 to 99% in comparison to a minimum of 97% for
&agr;1, but these differences were unevenly distributed along the
molecule. There was a particularly striking homology between rodent and
human sequences in the carboxyl terminal region. Binding of Goodpasture
autoantibodies to rat &agr;3(IV)NC1 was poor in comparison with other
species. Conclusions: Comparison of sequences and
binding casts doubt on the importance of the carboxyl-terminal region for
antibody binding, a region identified as a potential major epitope in
previous studies. Sequence comparisons suggest possible reasons for the
nephritogenicity of &agr;3(IV)NC1 in active models of anti-GBM disease.
Key words: autoantibody; autoantigen; collagen IV;
glomerular basement membrane; Goodpasture; xenotransplantation
ORIGINAL ARTICLES
Sequence analysis of the 'Goodpasture antigen' of mammals
Departments of Medicine andHaematology, Royal Postgraduate Medical School, London UK; Corresponding author at: Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
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