Inter-molecular epitope spreading does not lead to extension of autoimmunity beyond target tissue in autoimmune glomerulonephritis

PloS One
April RossYa-Huan Lou

Abstract

Inter-molecular epitope spreading during autoimmune pathogenesis leads to generation of new pathogenic epitopes on other autoantigens beyond the original one. It raises an important question as whether autoimmunity extends beyond the target tissues if new epitopes are on the molecules shared with other tissues. This study is aimed addressing this question in a rat anti-glomerular basement membrane (GBM) glomerulonephritis model induced by a T cell epitope of glomerulus-specific collagen4α3. We have demonstrated inter-molecular B cell epitope spreading. Four novel epitopes were first identified by screening a phage display random peptide library against autoantibodies isolated from the GBM of immunized rats. All four epitopes were derived from GBM proteins with three from laminins and one from collagen4α4. Three out of four synthetic peptides were nephritogenic. Importantly, two peptides from lamininα1 and lamininβ1, respectively, induced severe inflammation in glomeruli but not in the interstitial tissues, despite the presence of more abundant laminins in the tubular basement membranes. Our study suggests that surrounding tissues may display a lower or altered susceptibility to autoimmune inflammation. Thus, preventing extensio...Continue Reading

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Citations

Apr 25, 2021·Journal of the American Society of Nephrology : JASN·Cong-Rong ShenDorin-Bogdan Borza

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Methods Mentioned

BETA
phage display
ELISA

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