Specific removal of IgE by therapeutic immunoadsorption system.
A therapeutic immunoadsorption system was developed that can remove IgE effectively and specifically from the plasma of patients with an allergy or other hyper-IgE syndrome. The immunoadsorbent (IA) consists of immunoaffinity purified anti-IgE antibody (a-IgE ab) immobilized on controlled pore glass beads (50 nm pore size). Adsorption isotherms for IgE, which were reduced by the Freundlich adsorption equation, were obtained with IA that immobilized various amounts of a-IgE ab. An optimum amount of a-IgE ab to be immobilized was selected. IA worked sufficiently in a wide range of IgE concentrations. Clinical treatment requires an amount of 41 mg of IgE to be removed from a patient's plasma for 3 h. An IA for clinical use was designed to contain 10 g of the support binding 325 mg or more of the antibody. In fact, our study in vitro simulating a clinical case showed that serum IgE was removed by IA, as expected: the level decreased from 11,000 to 3000 U/ml after a 3 h perfusion (1 U = 2.3 ng). A very small amount of a-IgE ab (goat IgG) was found to be detached from IA by flowing plasma; the average level was 20 ng/ml, which seems to be safe. However, we installed the second column in a circuit that adsorbs a-IgE ab leaked into plasma, because the amounts of a-IgE ab infused into the patient must be minimized. The second column contained IgE immobilized on the same support, since IgE as a ligand adsorbed more a-IgE ab than did anti-goat IgG antibody. This is an effective and safe therapeutic immunoadsorption system and has been subjected to clinical tests.