Antigenic charge as a factor in resistance to immunosuppressive therapy.

This study examines the effects of methylprednisolone (MP) on the glomerular lesions induced by the injection of cationic bovine serum albumin (BSA) in rabbits. Male New Zealand white rabbits (n = 55) were treated with cationic BSA alone (n = 13), cationic BSA plus MP (n = 26), native BSA alone (n = 8), or native BSA plus MP (n = 8). Animals receiving BSA alone developed subepithelial immune complex deposits after injections of cationic BSA or mesangial immune complex deposits after injections of native BSA. Subepithelial deposits were inhibited in only 10 of 26 rabbits receiving MP and cationic BSA. Glomerular lesions occurred rather predictably in this group unless complete ablation of antibody production was achieved. Even minimal amounts of detectable antibody were sufficient to support the development of the full-blown renal lesion. Proteinuria was diminished in all animals receiving cationic BSA and MP in whom a beneficial histologic effect was observed. MP inhibited the development of mesangial deposits in all of the animals given native BSA. This inhibition was associated with almost complete ablation of anti-BSA antibody production in this group. Renal perfusion studies (n = 8) demonstrated that the beneficial effects of MP on the development of immune deposits were related to systemic immunosuppression and not to local structural alterations in the glomerulus. Our findings confirm that the pattern of immune response to native and cationic antigens differ. In addition, they demonstrate that cationic antigens appear to require only small amounts of free circulating antibody in order to produce glomerular immune complexes and cause proteinuria.