title: Autoantibodies and monoclonal antibodies directed to an immunodominant antigenic region of thyroglobulin interact with thyroperoxidase through an interspecies idiotype.
abstract: We investigated whether thyroglobulin (TG) autoantibodies (aAb) cross-react with thyroperoxidase (TPO) through an idiotypic structure using pooled normal human IgG (NhlgG) as a natural anti-idiotype reagent. Affinity-purified TG aAb from pooled IgG of patients with autoimmune thyroid disease were chromatographed on Sepharose-bound NhlgG. About one fourth of the loaded material bound to and eluted from the coupled gel. Eluted TG aAb were found reactive to TG and TPO and their TPO but not TG binding was strongly inhibited by molar excess of NhlgG. These TG aAb appeared to be mainly directed to an immunodominant TG antigenic region defined by TG monoclonal antibodies (mAb) from a single cluster of reactivity. These TG mAb were also found to recognize TPO and their binding to TPO but not TG was inhibited by molar excess of NhlgG as already observed with TG aAb. Taken together, these results indicated that TPO interacts with an idiotype present on human TG aAb and mouse TG mAb displaying a similar epitopic specificity; this interspecies idiotype is recognized by anti-idiotype antibodies present in NhlgG. Our results suggest that thyroid autoimmunity can be envisaged, at least in part, as a disturbance in interconnected idiotypic networks.
authors.affiliation: Unité 38 de l'Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Ruf
authors.forename: M
authors.initials: M
authors.lastname: Ferrand
authors.forename: J M
authors.initials: JM
authors.lastname: Durand-Gorde
authors.forename: P
authors.initials: P
authors.lastname: Carayon
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002846:Chromatography, Affinity; D003429:Cross Reactions; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007453:Iodide Peroxidase / Q000276:immunology*; D008297:Male; D051379:Mice; D013045:Species Specificity; D013954:Thyroglobulin / Q000276:immunology*; D013959:Thyroid Diseases / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; C056626:thyroid microsomal antibodies; D013954:Thyroglobulin; D007453:Iodide Peroxidase