Glomerular antibodies in lupus nephritis.
Lupus nephritis (LN) remains the most common severe manifestation of systemic lupus erythematosus (SLE) characterized by the presence of autoantibodies (Abs) that are believed to play a central role in the pathogenesis of LN. Among more than 100 Abs reported in SLE, only a few display a direct glomerular binding capacity. Such antiglomerular Abs are detected at the onset of the disease before antinuclear Abs detection and proteinuria, this detection is associated with the related autoantigen overexpression. Antiglomerular Abs are able to interfere with cell metabolism, to penetrate living cells, and to induce glomerular cell proliferation. In addition, antiglomerular Abs could be nephritogenic causing proteinuria, particularly when they cross-react with anti-dsDNA Abs. Antiglomerular Abs encompass anti-α-actinin, anti-laminin-1, antifibronectin, antimyosin, and anticollagen Abs. The pathogenic activity of anti-α-actinin Abs has been demonstrated in non-autoimmune mice after immunization with α-actinin, but not with dsDNA, leading to a SLE-like disease with proteinuria and glomerular immune complex deposition. Similarly, extracorporeal immunoabsorption to remove anti-laminin-1 Abs reduces kidney-Abs deposition and proteinuria in mice and humans proving their pathogenic effect. Altogether this suggests that antiglomerular Abs participate, at least at the beginning, in the glomerular immune complex deposition and in the kidney damage.
Hanrotel-Saliou
Catherine
C
Unit of Nephrology, Brest University Medical School Hospital, Brest, France.
Segalen
Isabelle
I
Le Meur
Yannick
Y
Youinou
Pierre
P
Renaudineau
Yves
Y
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology*; D049109:Cell Proliferation; D003429:Cross Reactions; D050533:Glomerular Basement Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D011507:Proteinuria
D001323:Autoantibodies; D001324:Autoantigens