Protein destabilizing agents induce polyreactivity and enhanced immunomodulatory activity in IVIg preparations.

Normal pooled human IVIg are produced using various blood protein fractionation technologies and as a result they may well differ in their biological properties. We have demonstrated that exposure of IVIg, for a period as short as 15 min, to protein-destabilizing agents like acidic pH, ROS or pro-oxidative ferrous ions dramatically increases the panel of recognized Ag including pro-inflammatory cytokines. We now show that exposure of IVIg to ferrous ions modifies some IgG molecules without denaturating them and enhances the protective activity of the preparation in experimental septic shock.