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Previous Volume 328:1599-1604 June 3, 1993 Number 22 Next

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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 subunit of the high-affinity IgE receptor (sFcRI).

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 sFcRI resulted in almost complete neutralization.

Conclusions Histamine-releasing IgG autoantibodies against the 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.

Source Information

From the St. John's Institute of Dermatology, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, St. Thomas's Hospital, London (M.H., D.M.F., C.E.H.G., M.W.G.), and the Departments of Immunopharmacology (J.H.) and Molecular Genetics (J.P.K.), Hoffmann-LaRoche, Nutley, N.J.

Address reprint requests to Dr. Greaves at the St. John's Institute of Dermatology, St. Thomas's Hospital, Lambeth Palace Rd., London, SE1 7EH, United Kingdom.

Full Text of this Article

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