title: Mycobacteria, an environmental enhancer of lupus nephritis in a mouse model of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of antibodies directed against self antigens. Immune complex glomerulonephritis (GN) is one of the most serious complications of this disorder and can lead to potentially fatal renal failure. The aetiology of SLE is complex and multifactorial, characterized by interacting environmental and genetic factors. Here we examine the nature of the renal pathology in mycobacteria-treated non-obese diabetic (NOD) mice, in order to assess its suitability as a model for studying the aetiopathogenesis of, and possible treatment options for, lupus nephritis (LN) in humans. Both global and segmental proliferative lesions, characterized by increased mesangial matrix and cellularity, were demonstrated on light microscopy, and lesions varied in severity from very mild mesangiopathic GN through to obliteration of capillary lumina and glomerular sclerosis. Mixed isotype immune complexes (IC) consisting of immunoglobulin G (IgG), IgM, IgA and complement C3c were detected using direct immunofluorescence. They were deposited in multiple sites within the glomeruli, as confirmed by electron microscopy. The GN seen in mycobacteria-treated NOD mice therefore strongly resembles the pathology seen in human LN, including mesangiopathic, mesangiocapillary and membranous subclasses of LN. The development of spontaneous mixed isotype IC in the glomeruli of some senescent NOD mice suggests that mycobacterial exposure is accelerating, rather than inducing, the development of GN in this model.
authors.affiliation: Autoimmunity Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown NSW, Australia.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Hawke
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Painter
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kirwan
authors.forename: Rosemary R
authors.initials: RR
authors.lastname: Van Driel
authors.forename: Alan G
authors.initials: AG
authors.lastname: Baxter
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology; D007105:Immune Complex Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008181:Lupus Nephritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008854:Microscopy, Electron; D014373:Tuberculin / Q000633:toxicity*
chemical_list: D000936:Antigen-Antibody Complex; D014373:Tuberculin