Pathogenesis of IgA nephropathy: <i>In vitro</i> activation of human mesangial cells by IgA immune complex leads to cytokine secretion

Abstract

Abstract IgA immune complex (IC) plays a crucial role in the pathogenesis of IgA nephropathy (IgAN). As IgA‐IC is not itself cytotoxic, other mediators may be involved in the pathogenesis. In order to elucidate the mechanisms by which IgA‐IC mediates renal injury in IgAN, the ability of IgA‐IC to ‘activate’ cultured human mesangial cells (HMC) was studied. HMC were incubated with nephritogenic IgA‐IC, containing a MOPC‐315 plasmacytoma‐derived IgA anti‐dinitrophenyl (DNP) and DNP‐conjugated bovine serum albumin. The cells showed morphological changes, an accelerated rate of proliferation, and increased production of interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), platelet activating factor (PAF) and generation of superoxide anion. The enhancement of IL‐1 and IL‐6 mRNA expression in HMC incubated with IgA‐IC was identified by dot blot analysis. Northern blot hybridization also demonstrated an augmented IL‐6 mRNA expression in HMC treated with IgA‐IC. These results suggest that nephritogenic IgA‐IC may amplify the proliferation of HMC and the production of immune/chemical mediators and superoxide anion thereby resulting in the renal lesions of IgAN.