Allergic manifestations as the results of a conditional autoimmune response

By means of repertoire cloning we have isolated human anti-IgE antibodies a s well as human anti-Fc epsilon RI antibodies. Whether the naturally occurr ing anti-IgE autoantibodies play a pathophysiological role may be disputed, but the beneficial role of recombinant anti-IgE antibodies as a therapeuti c agent has been shown. On the other hand, the natural antibodies isolated from an antibody library of a nonallergic individual against the Fc epsilon RI alpha -chain are anaphylactogenic, if Fc epsilon RI was not occupied. T hus, anti-Fc epsilon RI autoantibodies may be part of a conditional autoimm une reaction, leading to urticaria if local IgE is consumed, e.g. after an immediate reaction. Thus, anti-Fc epsilon RI antibodies may represent an am plification arm of the late reaction. The normal occurrence of anti-IgE and anti-IgE receptor autoantibodies may suggest that it might also be feasibl e to induce such autoantibodies by vaccination. In a mon key model using a mimotope of human IgE it was possible to induce a beneficial anti-IgE autoi mmune response. The actual epitope of the IgE molecule was then also molecu larly reconstructed by generating recombinant anti-idiotypic antibodies. Th ese antibodies also induced effectively an anti-IgE response in monkeys, su ggesting that not only mimotopes but also anti-idiotypic antibodies may be used to generate an autoimmune response. Both of our projects suggest that active immunization may be a new form of immunomodulation for the treatment of allergic disease. Copyright (C) 2001 S. Karger AG, Basel.