title: Non-immunoglobulin serum proteins prevent the binding of IgG from normal rats and from rats with Th2-mediated autoimmune glomerulonephritis to various autoantigens including glomerular antigens.
abstract: It is now well established in normal humans and mice that purification of IgG from serum unmasks their autoantibody activity. Mercuric chloride (HgCl2) induces in Brown-Norway (BN) rats a Th2-dependent polyclonal B cell activation, a huge increase in serum IgE and IgG1 concentrations, the production of numerous autoantibodies and an autoantibody-mediated glomerulonephritis. In the present study we have compared the IgG autoantibody activity in the serum and in the purified IgG fraction from normal and HgCl2-injected BN rats. IgG autoantibodies were found to be masked in normal serum by non-immunoglobulin (nonIg) serum proteins and, provided these IgG did not encounter normal serum proteins, they could bind to glomerular antigens as assessed by immunofluorescence in a unilateral perfused kidney model. As a consequence of HgCl2-induced polyclonal activation of B cells, IgG autoantibodies were no longer complexed to non-Ig serum proteins, they were easily detected in the serum and could therefore reach their glomerular target. However, these autoantibodies could still be blocked by normal non-Ig serum proteins not only in vitro but also in a unilateral perfused kidney model so that their binding to glomerular antigens could be prevented. These findings indicate that the ratio between autoantibody level and the amount of non-Ig serum proteins may be crucial in autoantibody-mediated autoimmune diseases.
authors.affiliation: INSERM U28, IFR 30, Hôpital Purpan, Faculté de Médecine Purpan, Toulouse, France.
authors.forename: E
authors.initials: E
authors.lastname: Druet
authors.forename: F
authors.initials: F
authors.lastname: Praddaude
authors.forename: P
authors.initials: P
authors.lastname: Druet
authors.forename: G
authors.initials: G
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions / Q000187:drug effects*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D001798:Blood Proteins / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D005260:Female; D005921:Glomerulonephritis / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D051379:Mice; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D001798:Blood Proteins; D016895:Culture Media, Serum-Free; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C038601:trinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D008627:Mercuric Chloride