PATHOGENESIS OF IGA NEPHROPATHY - IN-VITRO ACTIVATION OF HUMAN MESANGIAL CELLS BY IGA IMMUNE-COMPLEX LEADS TO CYTOKINE SECRETION

IgA immune complex (IC) plays a crucial role in the pathogenesis of Ig A nephropathy (IgAN). As IgA-IC is not itself cytotoxic, other mediato rs may be involved in the pathogenesis. In order to elucidate the mech anisms by which IgA-IC mediates renal injury in IgAN, the ability of I gA-IC to 'activate' cultured human mesangial cells (HMC) was studied. HMC were incubated with nephritogenic IgA-IC, containing a MOPC-315 pl asmacytoma-derived IgA anti-dinitrophenyl (DNP) and DNP-conjugated bov ine serum albumin. The cells showed morphological changes, an accelera ted rate of proliferation, and increased production of interleukin-1 ( IL-1), interleukin-6 (IL-6), platelet activating factor (PAF) and gene ration of superoxide anion. The enhancement of IL-1 and IL-6 mRNA expr ession in HMC incubated with IgA-IC was identified by dot blot analysi s. Northern blot hybridization also demonstrated an augmented IL-6 mRN A expression in HMC treated with IgA-IC. These results suggest that ne phritogenic IgA-IC may amplify the proliferation of HMC and the produc tion of immune/chemical mediators and superoxide anion thereby resulti ng in the renal lesions of IgAN.