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.

Development of Affinity Microparticles for Extracorporeal Blood Purification Based on Crystalline Bacterial Cell Surface Proteins

“…In comparison, a commercially available immunoadsorbent, IM‐PH (Asahi Medical, Tokyo, Japan), which binds immunoglobulins mainly by hydrophobic interactions, adsorbed 7 mg of IgG under the same experimental conditions. The IgG adsorption capacity of S‐layer based affinity microparticles was also significantly higher than the capacity of the commercially available Protein A‐silica affinity matrix Prosorba (Fresenius Hemocare, Bad Homburg, Germany) which binds about 8 mg IgG/g matrix (16). After the batch experiment, bound protein was eluted from the affinity microparticles at pH 3.5, and the eluate was subjected to SDS‐PAGE.…”

Plasmapheresis and Paraproteinemia: Cryoprotein‐Induced Diseases, Monoclonal Gammopathy, Waldenström's Macroglobulinemia, Hyperviscosity Syndrome, Multiple Myeloma, Light Chain Disease, and Amyloidosis

“…This is a semiselective procedure and usually does not require replacement fluid. A third type of procedure is immunoadsorption, in which the separated plasma can be processed using special antibody adsorption columns such as protein A columns, which remove IgG antibodies, or chemical affinity columns such as dextran sulfate with negative charges used to remove LDL cholesterol and antibodies ( 4). This is a selective procedure used to remove specific plasma pathogens and does not require replacement fluid.…”

Immunoadsorption of Immunoglobulins Alters Intracytoplasmic Type 1 and Type 2 T Cell Cytokine Production in Patients with Refractory Autoimmune Diseases

“…Because tissue damage in myasthenia gravis, pemphigus vulgaris, Goodpasture's syndrome, and hyperacute graft rejection is primarily caused by pathogenic autoantibodies, beneficial effects of IA in these disorders seem to be closely related to elimination of the disease‐specific autoantibody (1–5). However, in autoimmune diseases with predominant T cell‐dependent immunopathology such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), IA treatment induces clinical remissions as well (3,6–8). Thus, the clinical benefit of IA in predominantly T‐cell‐mediated autoimmune disorders is not solely attributable to direct effects of autoantibody elimination.…”