title: Serum IgG autoantibodies directed against the alpha chain of Fc epsilon RI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients?
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.
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Fiebiger
authors.forename: D
authors.initials: D
authors.lastname: Maurer
authors.forename: H
authors.initials: H
authors.lastname: Holub
authors.forename: B
authors.initials: B
authors.lastname: Reininger
authors.forename: G
authors.initials: G
authors.lastname: Hartmann
authors.forename: M
authors.initials: M
authors.lastname: Woisetschläger
authors.forename: J P
authors.initials: JP
authors.lastname: Kinet
authors.forename: G
authors.initials: G
authors.lastname: Stingl
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification; D015415:Biomarkers / Q000097:blood; D016466:CHO Cells; D002908:Chronic Disease; D006224:Cricetinae; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood* / Q000302:isolation & purification; D007313:Insecta; D046911:Macromolecular Substances; D017455:Receptors, IgE / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D012016:Reference Values; D014162:Transfection; D014581:Urticaria / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D017455:Receptors, IgE; D011994:Recombinant Proteins