Combined administration of IgA and IgG anti-Thy-1 antibodies enhances renal inflammation in rats

Background. IgA nephropathy (IgAN) is the most common type of immunological ly mediated glomerulonephritis (GN) and is characterized by deposition in t he glomerular mesangium of IgA together with C3, C5b-9, and properdin. In p atients, the codeposition of IgA. together with IgG and/or IgM can lead to a more progressive course of disease. In Wistar rats, mesangial proliferati ve GN can be induced by the injection of mouse IgG anti-Thy-1 antibodies (E R4G). In contrast, the administration of mouse IgA anti-Thy-1 antibodies (E R4A) to rats results in isolated hematuria without detectable albuminuria a nd without detectable complement deposition. Methods. To investigate the effect of the combination of IgA and IgG on glo merular injury, Wistar rats were injected with a limiting dose of ER4G in t he presence or absence of ER4A in a dose able to induce hematuria. Results. Although the limiting dose of ER4G or the dose of ER4A used did no t induce significant albuminuria, the combination of ER4G and ER4A resulted in a synergistic increase in albuminuria. Microhematuria occurred in rats receiving either ER4A or ER4G alone or in combination. Although both ER4A o r a limiting dose of ER4G induced minor increases in extracellular matrix e xpansion, the combination resulted in a pronounced, additive increased matr ix expansion. Conclusion. We conclude that in this model of IgA-mediated glomerulopathy, a selective complement-dependent synergistic renal injury is induced in Wis tar rats by glomerular codeposition of mouse anti-Thy-1 monoclonal isotypes .