Serum IgG autoantibodies directed against the a chain of Fc epsilon RI: A selective marker and pathogenetic factor for a distinct subset of chronic UrtiCaria patients?

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 (Fc epsilon RI), 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 Fc epsilon RI. In this study, we aimed to better characterize this anti-Fc epsilon RI alpha reactivity of CU patients using affinity-purified, IgE-depleted IgG fractions of such individuals (CU-IgG), Using immobilized, recombinant soluble Fc epsilon RI alpha as a reaction target for Western blot studies, we found that 12/32 (37%) CU-IgG serum samples exhibited IgG autoreactivity against Fc epsilon RI alpha. These findings were confirmed by experiments demonstrating that immunoblot-reactive, but not immunoblot-nonreactive, CU-IgG preparations precipitated the Fc epsilon RI alpha from Fc epsilon RI alpha gamma-transfected cells, No anti-Fc epsilon RI alpha 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-Fc epsilon RI alpha 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.