Accelerated autoantibody clearance by IVIG therapy

Recently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIG) in antibody‐mediated autoimmune disorders is based on an accelerated catabolism of autoantibodies due to saturation of FcRn. In the present study, we determined the magnitude and time course of this effect in a computer simulation to see whether this mechanism may indeed explain clinical observations. A pharmacokinetic model for IgG clearance was established in which concentration changes were calculated in small time steps. To validate the model we performed in vivo experiments with mice. A computational simulation accurately predicted the magnitude of the observed in vivo effect of IVIG administration on endogenous IgG levels. For human patients our model predicted a gradual decrease in autoantibody levels after IVIG administration (2 g/kg) with a maximum reduction of about 25% after 3–4 weeks and a duration of several months. This corresponds well to the effects of IVIG therapy observed in two patient studies: one on calcium‐channel autoantibodies by Bain et al . ( Neurology 1996; 47: 678–683) and another on ANCA by Jayne et al . ( J Autoimmunity 1993; 6: 207–219). In conclusion, accelerated IgG clearance can explain a modest decrease in autoantibody levels observed in several patient studies. However, in some other clinical studies larger or more rapid effects have been observed, which can not be explained by accelerated clearance, suggesting that IVIG can also reduce autoantibody levels via other mechanisms such as down‐regulation of antibody production or neutralization by anti‐idiotypic antibodies.