title: Natural anti-FcepsilonRIalpha autoantibodies may interfere with diagnostic tests for autoimmune urticaria.
abstract: IgG autoantibodies against the alpha-chain of the high affinity IgE receptor are claimed to play a pathogenetic role in autoimmune urticaria. The best methods for detection of functional autoantibodies are currently the autologous serum skin test and the basophil histamine release assay. A simplified and feasible screening test would facilitate the diagnosis of autoimmune urticaria. Here we offer an explanation for the difficulties in establishing a screening test for autoantibodies directed against the alpha-chain of the high affinity IgE receptor in autoimmune urticaria. Identical autoantibodies in chronic urticaria patients and healthy donors belonging to the natural autoantibody repertoire were found by sequence analysis of anti-alpha-chain autoantibodies isolated by repertoire cloning from antibody libraries. These natural autoantibodies bound to the receptor and triggered histamine release but only if IgE was previously removed from the receptor. Diagnostic assays used for detection of antibodies directed against the IgE receptor may require signal comparison with and without the artificial removal of IgE, immune complexes, and complement in order to avoid false positive or negative results. After IgE removal diagnostic tests will detect natural autoantibodies against the high affinity IgE receptor regardless of whether they are pathogenic or not.
authors.affiliation: Institute of Immunology, Sahlihaus 1, Inselspital, CH-3010 Bern, Switzerland.
authors.forename: Jana M
authors.initials: JM
authors.lastname: Pachlopnik
authors.forename: Michael P
authors.initials: MP
authors.lastname: Horn
authors.forename: Michaela
authors.initials: M
authors.lastname: Fux
authors.forename: Markus
authors.initials: M
authors.lastname: Dahinden
authors.forename: Michèle
authors.initials: M
authors.lastname: Mandallaz
authors.forename: Dominique
authors.initials: D
authors.lastname: Schneeberger
authors.forename: Lucia
authors.initials: L
authors.lastname: Baldi
authors.forename: Monique
authors.initials: M
authors.lastname: Vogel
authors.forename: Beda M
authors.initials: BM
authors.lastname: Stadler
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Miescher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology; D003951:Diagnostic Errors; D006632:Histamine / Q000097:blood; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014581:Urticaria / Q000175:diagnosis* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007141:Immunoglobulin Fc Fragments; D017455:Receptors, IgE; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D006632:Histamine