Article

Autoimmune mechanisms in chronic idiopathic urticaria.

Asthma and Allergic Disease Center, Carter Center for Immunology Research, University of Virginia, Charlottesville, Va.
The Journal of allergy and clinical immunology (Impact Factor: 12.05). 06/2012; 130(3):814-816.e4. DOI:10.1016/j.jaci.2012.04.037
Source: PubMed
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    ABSTRACT: Recent data suggest that a subpopulation of patients with chronic urticaria have an autoimmune disorder that is caused by the presence of antibodies to the IgE receptor. The actual incidence of these antibodies is uncertain. We sought to assess the incidence of autoimmunity to the IgE receptor in patients with chronic urticaria and to compare functional and binding assays. We isolated skin mast cells and studied a large number of patient sera (68) for their ability to activate these cells and isolated basophils. We then compared the results with those obtained by immunoblotting using cloned alpha-subunit of the IgE receptor. Sera from patients with chronic urticaria released significant histamine (> 15% of basal) on incubation with basophils (48%) and mast cells (46%). By immunoblotting we obtained positive results in 64% of subjects tested and also identified a small subpopulation that is active on cells but does not bind Fc(epsilon)RIalpha. Our data suggest that approximately 45% to 50% of patients with chronic urticaria have a cutaneous autoimmune disorder. Immunoblotting may provide a rapid screening method for anti-Fc(epsilon)RIalpha detection in such patients.
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    ABSTRACT: While it is well established that acute allergic urticaria is caused by degranulation of skin mast cells occurring after allergen/IgE-dependent cross-linking of high affinity IgE receptors (FcepsilonRI), the pathophysiologic mechanisms operative in chronic urticaria (CU) are less well understood. Some evidence points to the existence of histamine-releasing activity in the serum of CU patients which possibly acts via triggering of FcepsilonRI. In this study, we aimed to better characterize this anti-FcepsilonRIalpha reactivity of CU patients using affinity-purified, IgE-depleted IgG fractions of such individuals (CU-IgG). Using immobilized, recombinant soluble FcepsilonRIalpha as a a reaction target for Western blot studies, we found that 12/32 (37%) CU-IgG serum samples exhibited IgG autoreactivity against FcepsilonRI- alpha. These findings were confirmed by experiments demonstrating that immunoblot-reactive, but not immunoblot-nonreactive, CU-IgG preparations precipitated the FcepsilonRIalpha from FcepsilonRI- alphagamma-transfected cells. No anti-FcepsilonRIalpha reactivity was observed in IgG fractions from atopic dermatitis (AD) patients (0/15) or healthy control individuals (CO:0/15). As opposed to the selective occurrence of IgG anti-Fc epsilon RI alpha autoantibodies in CU patients, IgG anti-IgE antibodies were detected in all groups investigated (CU: 69%; AD: 73%; CO: 26%). While both types of autoantibodies can exhibit histamine-releasing properties, not all of the autoantibodies proved to be functional in vitro. Our results indicate that the occurrence of IgG anti-FcepsilonRIalpha reactivity defines an autoimmune-mediated subentity of CU and provide a basis for the development of new diagnostic procedures and, perhaps, therapeutic strategies for this disease.
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