title: Down-regulation of pathogenic autoantibody response in a slowly progressive Heymann nephritis kidney disease model.
abstract: In the present article, we describe an antigen-specific down-regulation of a pathogenic autoantibody (aab)-mediated disease process in an experimental autoimmune kidney disease in rats called slowly progressive Heymann nephritis (SPHN). This autoimmune disease is initiated and maintained by pathogenic immunoglobulin G (IgG) autoantibodies (aabs), which cause an immune-complex (IC) glomerulonephritis associated with proteinuria. We achieved down-regulated pathogenic aab response in SPHN rats by injections of an IC containing the native nephritogenic antigen and specific high-titred nonpathogenic IgM aabs, in antigen excess. The injected IC increased the level of circulating nonpathogenic IgM aabs; the increased levels of specific IgM aabs in turn facilitated the removal of the injected altered nephritogenic and liberated autoantigens from the renal tubules and greatly diminished the production of pathogenic aabs and the build up of immune deposits in the glomeruli. While animals treated early had advantages over rats whose kidney disease was well established before treatment; animals treated late into the disease still manifested noticeable improvements in similar areas, i.e. with lessened proteinuria, kidney lesion reduction and a decreased pathogenic aab response. At the end of the experiment at 29 weeks, 80% of all the treated rats had insignificantly low levels of circulating IgG aabs, indicating cessation of pathogenic aab production and corresponding termination of the disease process. In contrast, most untreated rats with the kidney disease still had high levels of circulating pathogenic aabs at the end of the experiment, which maintained disease progression.
authors.affiliation: Department of Surgery, University of Calgary, Health Sciences Centre 2802, 3330 Hospital Dr N.W., Calgary, Alberta, Canada T2N 4N1. barabas@ucalgary.ca
authors.forename: Arpad Z
authors.initials: AZ
authors.lastname: Barabas
authors.forename: Chad D
authors.initials: CD
authors.lastname: Cole
authors.forename: Arpad D
authors.initials: AD
authors.lastname: Barabas
authors.forename: Rene
authors.initials: R
authors.lastname: Lafreniere
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000276:immunology*; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D005921:Glomerulonephritis / Q000150:complications / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence / Q000379:methods; D011507:Proteinuria / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M