STUDY OF EHS TYPE-IV COLLAGEN LACKING GOODPASTURES EPITOPE IN GLOMERULONEPHRITIS IN RATS

Citation
Wk. Bolton et al., STUDY OF EHS TYPE-IV COLLAGEN LACKING GOODPASTURES EPITOPE IN GLOMERULONEPHRITIS IN RATS, Kidney international, 47(2), 1995, pp. 404-410
Citations number
40
Categorie Soggetti
Urology & Nephrology
Journal title
ISSN journal
00852538
Volume
47
Issue
2
Year of publication
1995
Pages
404 - 410
Database
ISI
SICI code
0085-2538(1995)47:2<404:SOETCL>2.0.ZU;2-R
Abstract
The Goodpasture's epitope has been mapped to the alpha(3) non-collagen ous chain (NC1) of type (IV) collagen [alpha(3)col(IV)]. We have devel oped a model of experimental autoimmune glomerulonephritis (EAG) in ra ts immunized once with collagenase solubilized GBM (csGBM). Engelbreth -Holm-Swarm (EHS) tumor contains abundant col(IV) with little or no al pha(3)col(IV). To test the hypothesis that antigens related to Goodpas ture epitope are required to produce EAG in our model, we immunized ra ts once with 40 mu g csEHS. Positive controls immunized with csGBM dev eloped typical EAG with GBM bound antibody, proteinuria, and glomerulo nephritis. EHS rats developed circulating and bound antibody to mesang ium and tubular basement membrane with minimal GBM deposits, but did n ot develop proteinuria or glomerulonephritis. Although circulating ant ibody in EHS rats bound to csGBM by ELISA, there was no binding in ELI SA to M2 antigen containing the Goodpasture epitope while EAG rat's se rum did bind. By Western blot with antisera to Goodpasture epitope, EH S antigen was less complex than GBM in the monomer/dimer regions and a ppeared to lack NCI corresponding to alpha(3)col(IV). Blotting with se ra from EHS rats demonstrated reactivity to various components of GBM but not to alpha(3)col(IV). EAG sera and renal eluates bound to alpha( 3)col(IV). EAG rats evidenced cell mediated immunity while EHS rats di d not (stimulation index EHS 1.1, EAG rats 8.0). These studies show th at the development of antibody to col(nr) in a setting conducive to EA G does not cause EAG in the absence of alpha(3)col(TV) NC1, that the a ntibody response in EHS rats was not associated with a cellular respon se to the antigen and that an epitope on the same NC1 alpha(3)col(IV) which contains the Goodpasture epitope appears necessary to induce EAG in this model These studies further implicate the alpha(3)col(IV) as a pathogenetic factor in the development of Goodpasture syndrome in hu mans as well as a marker of disease.