Abnormalities in the regulation of human IgE synthesis

Prior to their demonstration that human allergic antibody is confined primarily to a unique immunoglobulin class, undefined genetic and environmental factors were suspected of determining the production of reaginic antibody in some persons but not in others. The elucidation of the molecular nature of this antibody made possible subsequent incisive studies on events controlling the initiation and regulation of IgE antibody synthesis. During the past 11 years in vivo studies in rodents have defined a fundamental role for thymus-derived cells in the regulation of IgE production. It would obviously be helpful to know if similar controls operate in man, since the goal of many investigators of human IgE-mediated hypersensitivity is to develop ways to manipulate the IgE antibody response so that it can be 'turned off' in those diseases where it appears to have a primary role. The evidence that excessive human IgE production is due to faulty immunoregulation is primarily circumstantial. Increased IgE production has been detected with high frequency in certain of the primary immunodeficiency syndromes characterized by partial but not complete deficiencies in thymus-dependent immune function. These include the Wiskott-Aldrich, Nezelof, DiGeorge and Hyper IgE syndromes. In these conditions it has been postulated but not proved that the increased IgE is due to a deficiency of T cells regulating that response. Similar postulates have been made for the human atopic diseases, particularly in atopic dermatitis, where subtle evidence of depressed cellular immunity has been demonstrated. However, direct demonstration of such a deficiency must await an appropriate model for investigating the control of human IgE synthesis. Since in vivo studies analogous to those done in rodents are not possible in man, efforts have been made by several groups to develop in vitro methods for detecting IgE synthesis by blood mononuclear cells.