Immune Modulation Associated with Extracorporeal Immunoadsorption Treatments Utilizing Protein A/Silica Columns

Abstract: The Prosorba column is designed for the removal of IgG and IgG containing immune complexes from plasma. Clinical studies employing patients presenting with idiopathic thrombocytopenic purpura (ITP) indicate that this new form of therapy is effective in approximately 40% of treated patients. Responding patients exhibit a significant increase in platelet numbers associated with decreases in antiplatelet antibody and immune complexes suggesting the induction of immune modulation. Preliminary studies indicate that ITP patients presenting with antiplatelet IgG antibody are those most likely to respond. In addition, this subgroup of ITP patients also exhibit elevated levels of antiidiotypic IgG antibody, which may contribute to an exacerbation of the autoimmune process due to antigen mimicry of the platelet autoantigen. Interestingly, antiidiotypic IgG antibody levels appear to decrease in association with antiplatelet IgG autoantibody levels suggesting that removal of immune complexes composed of IgG autoantibody and platelet autoantigen and/or antiidiotypic IgG antibody may be related to the observed clinical responses. Additional studies with alloimmune patients refractory to platelet transfusion suggest that transfused platelet retention time may be increased as a consequence of immunoadsorption therapy. This clinical response appears to be related to decreases in IgG alloantibody, again suggesting the induction of immune modulation. Alloimmune thrombocytopenic patients also appear to present with elevated levels of antiidiotypic IgG antibody which may contribute to an exacerbation of the alloimmune process due to antigen mimicry of platelet alloantigen(s). Preliminary studies indicate that both IgG alloantibody and corresponding antiidiotypic IgG antibody levels appear to decrease during immunoadsorption therapy, which suggests that removal of these antibodies, possibly in the form of immune complexes, may be related to clinical responses. Finally, studies in rheumatoid arthritis patients suggest that immunoadsorption therapy may be of clinical benefit in this autoimmune disorder. Consistent with the results observed above, preliminary studies in patients responding to immunoadsorption treatments again suggest that there is a concomitant decrease in idiotypic IgG (rheumatoid factor) and antiidiotypic IgG antibodies levels during therapy.