AUTOANTIBODIES AGAINST THE HIGH-AFFINITY IGE RECEPTOR AS A CAUSE OF HISTAMINE-RELEASE IN CHRONIC URTICARIA

Background. Most urticarias are induced by vasoactive mediators such a s histamine released from mast cells. Although mast cells are activate d by allergens through cross-linking of cell-surface-bound IgE, this m echanism does not appear to explain most cases of chronic urticaria, w hich, when allergic, infectious, drug-induced, or physical causes cann ot be identified, are classified as idiopathic. Methods. We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal inj ection of autologous serum caused a wheal-and-flare response. Serum fr om four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect t o the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation o f the soluble extracellular domain of the a subunit of the high-affini ty IgE receptor (sFcepsilonRIalpha). Results. The histamine-releasing activity of the serum was abolished by passive sensitization of basoph ils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all f our patients. Preincubation of the serum and isolated IgG with sFcepsi lonRIalpha resulted in almost complete neutralization. Conclusions. Hi stamine-releasing IgG autoantibodies against the a subunit of the high -affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE rec eptors may be an important mechanism in the pathogenesis of chronic ur ticaria and other diseases mediated by mast cells.