title: Human anti-FcepsilonRIalpha autoantibodies isolated from healthy donors cross-react with tetanus toxoid.
abstract: Natural antibodies (Ab) reacting with self antigens have been shown to be present in all individuals. These autoantibodies (auto-Ab) can be either pathogenic or non-pathogenic. Auto-Ab reacting with the alpha-subunit of the high-affinity receptor for IgE (FcepsilonRIalpha) have been implicated in the pathogenesis of a subset of patients with chronic idiopathic urticaria (CIU). Intravenous immunoglobulin (IVIg) preparations have been used with variable clinical benefit in the treatment of these patients. Here we show that anti-FcepsilonRIalpha auto-Ab are present in a therapeutic IVIg preparation as well as in atopic and chronic urticaria patients and healthy individuals. We affinity-purified the anti-FcepsilonRIalpha Ab from an IVIg preparation using recombinant FcepsilonRIalpha. Interestingly, these anti-FcepsilonRIalpha auto-Ab showed no evidence of histamine release but strongly cross-reacted with an external antigen, tetanus toxoid (TTd) with a higher affinity for TTd than for the FcepsilonRIalpha. Since the cross-reacting Ab are non-anaphylactogenic, there is no evidence that TTd immunization may contribute to the pathogenesis of CIU. However, our results may indicate that the anti-FcepsilonRIalpha auto-Ab belong to the natural Ab and serve as the parental Ab for some anti-TTd Ab.
authors.affiliation: Institute of Immunology and Allergology, University of Bern, Switzerland. michael.horn@insel.ch
authors.forename: M P
authors.initials: MP
authors.lastname: Horn
authors.forename: T
authors.initials: T
authors.lastname: Gerster
authors.forename: B
authors.initials: B
authors.lastname: Ochensberger
authors.forename: T
authors.initials: T
authors.lastname: Derer
authors.forename: F
authors.initials: F
authors.lastname: Kricek
authors.forename: M H
authors.initials: MH
authors.lastname: Jouvin
authors.forename: J P
authors.initials: JP
authors.lastname: Kinet
authors.forename: T
authors.initials: T
authors.lastname: Tschernig
authors.forename: M
authors.initials: M
authors.lastname: Vogel
authors.forename: B M
authors.initials: BM
authors.lastname: Stadler
authors.forename: S M
authors.initials: SM
authors.lastname: Miescher
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D016466:CHO Cells; D006224:Cricetinae; D003429:Cross Reactions; D005312:Fetal Blood / Q000276:immunology; D006636:Histamine Release; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007231:Infant, Newborn; D051379:Mice; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D017455:Receptors, IgE; D011994:Recombinant Proteins; D013745:Tetanus Toxoid