Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease

Abstract

The experimental models of Heymann nephritis (HN) and slowly progressive Heymann nephritis (SPHN) give us rare opportunities to investigate the etiologies and pathogenesis of two immunopathological processes in rats leading to: (1) autoimmune disease, where the autoimmune disease HN and SPHN is initiated and maintained by cross-reactive pathogenic IgG autoantibodies (aabs) directed against the renal proximal convoluted tubules' brush border (BB) cells – where the nephritogenic antigen (ag) is produced and localized – damaging and releasing BB associated nephritogenic ag into the circulation which in turn contributes to continuation of the autoimmune disease; and (2) immune complex glomerulonephritis, where the glomerular injury is initiated, proceeding into a chronic progressive disease by depositing immune complexes (ICs) – made up of a glomerular epithelial cell produced endogenous nephritogenic ag and the developing pathogenic IgG aab directed against the nephritogenic ag, and complement components – on the epithelial side of the glomerular basement membrane. We also observed how the normally functioning immune system is able to avert autoimmune disease developments by circulating specific non-pathogenic IgM aabs clearing the system of intracytoplasmic ags released from cells at the end of their life spans or following damage by toxic agents. We also described how an autoimmune disease SPHN can be prevented and when present terminated by the implementation of a new vaccination technique we have developed and call modified vaccination technique. By increasing the specific IgM aab production against the native nephritogenic ag – by injecting ICs made up of: [nephritogenic ag X homologous anti-nephritogenic ag IgM ab] in slight ag excess into SPHN rats – pathogenic IgG aab producing native and modified nephritogenic ags were removed from the circulation and termination of the autoimmune disease causing immune events was achieved. Even though HN and SPHN are not well-known disease models, their studies are important because the etiologies and pathogenesis of two conditions – that can also occur in humans, namely autoimmune diseases and membranous glomerulonephritis – can be simultaneously investigated.