IgG4 and hyposensitization

The mechanism of action of hyposensitization is still unclear. Probably, allergen-blocking antibodies have some effect, in particular in insect venom allergy, but it is likely that other mechanisms are operative as well. With the types of treatment currently available suppression of the production of specific IgE antibodies does not seem to be a dominating factor. In view of the presumed minor contribution of allergen-blocking antibodies in inhalant allergy, it is as yet impossible to define the role of IgG4 antibodies other than quantitatively: It is the main allergen-blocking antibody! There is no conclusive evidence that the IgG4 is the exclusive allergen-blocking antibody in immediate type allergy. However, its main biologic significance might well be on a completely different level, viz. prevention of immune complex disease. The production of non-complement fixing antibodies, unable to form large complexes due to functional monovalency, during prolonged antigenic exposure seems to provide adequate protection against complement-induced damage and other sequela of precipitating immune complexes that can be expected from a persistent production of IgG1. The rare occurrence of immune complex induced disorders during hyposensitization therapy is possibly a result of this phenomenon.