title: Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis.
abstract: In a rabbit model, we have previously reported evidence for a pathogenic role of streptococcal IgG Fc-binding proteins (IgGFcBP) in poststreptococcal glomerulonephritis (PSGN). These proteins, of the M protein family, were shown to trigger anti-IgG production and enhance renal deposition of IgG and/or immune complexes (ICs), with resulting activation of complement and cytokine cascades. In the present study, type M12/emm12, group A streptococci (GAS) were found often to bind artificial ICs, viz. peroxidase-anti-peroxidase rabbit IgG (PAP) or tetanus toxoid-anti-tetanus human IgG (TAT), rather than monomeric IgG. Animals injected with each of four IC binding clinical isolates (from patients with scarlet fever or PSGN) showed pronounced inflammatory and degenerative glomerular changes, morphologically similar to human PSGN, with membrane thickening and IgG and complement C3 deposition, as well as secretion of IL-6 and TNF-α by mesangial and endothelial cells. In contrast, non-binding strains (two from asymptomatic carriers and one from a PSGN case) failed to trigger any renal changes. Only the IC binding strains induced elevated titres of anti-IgG. Though the streptococcal binding component(s) has not been demonstrated, the selective binding of ICs by type M12/emm12 strains appears important for the well-known, marked nephritogenic potential of this GAS type.
authors.affiliation: Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
authors.forename: Larissa
authors.initials: L
authors.lastname: Burova
authors.affiliation: Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
authors.forename: Peter
authors.initials: P
authors.lastname: Pigarevsky
authors.affiliation: Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Duplik
authors.affiliation: Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
authors.forename: Vlada
authors.initials: V
authors.lastname: Snegova
authors.affiliation: Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Suvorov
authors.affiliation: Department of Laboratory Medicine, University of Lund, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Schalen
authors.affiliation: Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
authors.forename: Artem
authors.initials: A
authors.lastname: Totolian
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D001485:Basement Membrane / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology*; D002353:Carrier State / Q000382:microbiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D005838:Genotype; D005921:Glomerulonephritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007672:Kidney Cortex / Q000276:immunology / Q000382:microbiology; D011485:Protein Binding; D011817:Rabbits; D012541:Scarlet Fever / Q000382:microbiology; D013045:Species Specificity; D013290:Streptococcal Infections / Q000276:immunology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C034284:IgG Fc-binding protein, Streptococcus; D007074:Immunoglobulin G; C014689:streptococcal M protein