title: Anti-FcepsilonRIalpha autoantibodies in autoimmune-mediated disorders. Identification of a structure-function relationship.
abstract: Anti-FcepsilonRIalpha autoantibodies (autoAbs) occur and may be of pathogenetic relevance in a subset of chronic urticaria (CU) patients. To analyze the prevalence and magnitude of the humoral anti-FcepsilonRIalpha response in cohorts of CU patients compared with individuals suffering from classic skin- related (auto)immune diseases, we developed an ELISA system for the measurement of anti-FcepsilonRIalpha autoAbs in nonfractionated serum samples. Results obtained using this assay correlated well with those generated by Western blotting. We found IgG anti-FcepsilonRIalpha autoreactivity in 38% of CU patients but not in atopic dermatitis patients, psoriatics, or healthy individuals. We frequently detected anti-FcepsilonRIalpha autoAbs in pemphigus vulgaris (PV, 39%), dermatomyositis (DM, 36%), systemic lupus erythematosus (SLE, 20%), and bullous pemphigoid (BP, 13%). While the autoAb titers in DM, SLE, BP, and PV were similar to those encountered in CU patients, only anti-FcepsilonRIalpha+ CU serum specimens displayed pronounced histamine-releasing activity. The anti-FcepsilonRIalpha autoAbs in CU patients belong predominantly to the complement-fixing subtypes IgG1 and IgG3, whereas in DM, PV, and BP, they were found to be mainly of the IgG2 or IgG4 subtype. Complement-activating properties of anti-FcepsilonRIalpha autoAbs can indeed be of pathogenetic relevance, because C5a receptor blockade on basophils as well as decomplementation reduced drastically the histamine-releasing capacity of most anti-FcepsilonRIalpha-reactive CU sera. As a consequence, therapeutic efforts in CU should aim at altering not only the quantity but also the complement-activating properties of IgG anti-FcepsilonRIalpha autoAbs.
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), University of Vienna Medical School, A-1090 Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Fiebiger
authors.forename: F
authors.initials: F
authors.lastname: Hammerschmid
authors.forename: G
authors.initials: G
authors.lastname: Stingl
authors.forename: D
authors.initials: D
authors.lastname: Maurer
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology*; D001491:Basophils / Q000378:metabolism; D002908:Chronic Disease; D015936:Complement C5a / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006636:Histamine Release; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D014581:Urticaria / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015936:Complement C5a