Combined glomerular deposition of polymeric rat IgA and IgG aggravates renal inflammation

Background. IgA nephropathy (IgAN) is characterized by deposition in the gl omerular mesangium of IgA together with C3, C5b-9, and properdin. IgG depos ition as a risk factor in IgAN was recently confirmed by a long-term follow -up of patients with IE;AN. We previously reported on an acute model of IgA -mediated glomerular inflammation in Wistar rats. Methods. To investigate the effect of the combination of IgA and IgG on glo merular injury, Wistar rats were injected with a minimum dose of rat IgG in the presence or absence of a subnephritogenic dose of polymeric rat IgA. S ubsequently, glomerular complement activation, influx of inflammatory cells , proteinuria, and hematuria were assessed. Results. Administration of IgG to the rats resulted in maximal proteinuria of 20.3 +/- 12.1 mg/24 h on day 2 and an absence of overt glomerular inflam mation. Administration of polymeric rat IgA antibodies to rats resulted in hematuria with a moderate mesangial complement deposition. In the combinati on group, however, glomerular deposition of C5b-9 was dramatically increase d. This was accompanied by increased proteinuria as compared with rats rece iving IgA or IgG antibody injections alone on day 7. Microhematuria occurre d in rats receiving either polymeric rat IgA or IgG alone or the combinatio n. While both rat IgG and polymeric IgA induced minor mesangial cell (MC) p roliferation and MC lysis, the combination resulted in a pronounced, signif icant increased percentage of aneurysm formation on day 7 after injection. Conclusions. We conclude that in this model of IgA-induced glomerulopathy, a selective, complement-dependent glomerular inflammation is induced in Wis tar rats by glomerular codeposition of rat isotypic monoclonal antibodies.