Search

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.

Extracorporeal immunoadsorption of plasma to remove IgG and circulating immune complexes (CIC) was evaluated as a therapy for adults with treatment-resistant immune thrombocytopenic purpura (ITP). Seventy-two patients with initial platelet counts less than 50,000/microL who had failed at least two other therapies were studied. They received an average of six treatments of 0.25 to 2.0 L plasma per procedure over a 2- to 3-week period using columns of staphylococcal protein A-silica (PROSORBA immunoadsorption treatment columns; IMRE Corp, Seattle, WA). The treatments caused an acute increase in the platelet count to greater than 100,000/microL in 18 patients and to 50,000 to 100,000/microL in 15 patients. The median time to response was 2 weeks. Responses were transient (less than 1 month duration) in seven of those patients (10%), but no additional relapses were reported over a follow-up period of up to 26 months (mean of 8 months). Clinical responses were associated with significant decreases in specific serum platelet autoantibodies (including anti-glycoprotein IIb/IIIa), platelet-associated Ig, and CIC. Thirty percent of treatments were associated with transient mild to moderate side effects usually presenting as a hypersensitivity-type reaction. Continued administration of failed therapies for ITP, which always included low-dose corticosteroids (less than or equal to 30 mg/d), had no demonstrable influence on the effectiveness of immunoadsorption treatment but did depress the incidence and severity of side effects. The degree of effectiveness of protein A immunoadsorption therapy in patients with treatment-resistant ITP is promising and further controlled studies in this patient population are warranted.

A relationship is described between the interaction of circulating immune complexes (CIC) from plasma with staphylococcal protein A immunoadsorption treatment columns and modulation of antibody responses related to the specific CIC. Eluates from the initial immunoadsorption columns used to treat a series of patients with breast adenocarcinoma, cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS), or immune thrombocytopenic purpura (ITP) were evaluated for disease-specific CIC containing Lex glycosphingolipid (Lex gl) adenocarcinoma-associated antigens or platelet autoantibody (anti-GPIIb/IIIa), together with the corresponding neutralizing antibody [anti-F(ab')2], and for nonspecific CIC containing cytomegalovirus (CMV) or herpes simplex virus type 1 (HSV-1) antigens. In addition, the levels of antibodies directed against CMV, HSV-1, Lex gl, and GPIIb/IIIa antigens, as well as anti-F(ab')2 antibodies, were compared in pretreatment and posttreatment serum samples. Columns used to treat breast adenocarcinoma patients contained only Lex gl CIC, and the only immunologic change observed after treatment was significant increases in anti-Lex gl antibodies in some patients. Columns used to treat C-TTP/HUS patients contained anti-GPIIb/IIIa-anti-F(ab')2 CIC, in addition to Lex gl CIC. After treatment, significant increases in anti-Lex gl and anti-F(ab')2 antibodies and significant decreases in anti-GPIIb/IIIa antibodies were observed in some patients. Columns used to treat ITP patients only exhibited anti-GPIIb/IIIa-anti-F(ab')2 CIC, and after treatment only decreases in anti-GPIIb/IIIa and increases in anti-F(ab')2 antibodies were observed in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)