Modulation of the host response in human schistosomiasis. III. Blocking antibodies specifically inhibit immediate hypersensitivity responses to parasite antigens.

Abstract

Mechanisms for modulating the host's immune response in human Schistosomiasis mansoni have been described for delayed hypersensitivity responsiveness and antibody production. Since clinical symptoms of immediate hypersensitivity (i.e. allergic reactivity) are rare in schistosomiasis despite the presence of parasite-specific immunoglobulin E, circulating parasite antigen, and normal numbers of basophils and mast cells in infected patients, it seemed likely that there was host modulation of immediate hypersensitivity responsiveness as well. Using an in vitro basophil histamine release assay we have shown that basophils from fifteen patients with S. mansoni infections are sensitized with schistosome-specific immunoglobulin E and will release histamine in an antigen-dose-dependent manner when challenged with a soluble adult worm antigen. This histamine release was suppressed by autologus, but not normal serum. Fractionation of the serum over staphylococcal protein A and antigen affinity columns identified an immunoglobulin G parasite-specific `blocking antibody', analogous to blocking antibodies elicited during immunotherapy of atopic patients, as being responsible for the modulation of this immediate hypersensitivity responsiveness in vitro. Blocking antibody specificity varied from patient to patient, an observation suggesting that different allergens were being recognized by different individuals. These studies demonstrate that in addition to the immunoregulatory mechanisms previously described in patients with schistosome infections, there is host modulation of immediate hypersensitivity responsiveness that appears to involve specific immunoglobulin G blocking antibodies.