Autoantibodies against the High-Affinity IgE Receptor as a Cause of Histamine Release in Chronic Urticaria

Abstract

Background: Most urticarias are induced by vasoactive mediators such as histamine released from mast cells. Although mast cells are activated by allergens through cross-linking of cell-surface-bound IgE, this mechanism does not appear to explain most cases of chronic urticaria, which, when allergic, infectious, drug-induced, or physical causes cannot be identified, are classified as idiopathic. Methods: We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal injection of autologous serum caused a wheal-and-flare response. Serum from four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect to the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation of the soluble extracellular domain of the α subunit of the high-affinity IgE receptor (sFcεRIα). Results: The histamine-releasing activity of the serum was abolished by passive sensitization of basophils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all four patients. Preincubation of the serum and isolated IgG with sFcεRIα resulted in almost complete neutralization. Conclusions: Histamine-releasing IgG autoantibodies against the α subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells., Chronic urticaria is a common skin disorder characterized by recurrent, transitory, itchy wheals. It is known that the binding of antigen (allergen) to antigen-specific IgE on mast cells and basophils causes the cells to degranulate, resulting in the release of histamine and other vasoactive mediators, which in turn evoke the clinical symptoms 1 , 2 . However, no specific allergic trigger for mast-cell or basophil activation has been identified in most patients with chronic urticaria 3 . It has been shown that in the majority of patients with severe chronic urticaria, intradermal injection of autologous serum elicits an immediate wheal-and-flare response and mast-cell… © 1993, Massachusetts Medical Society. All rights reserved.