title: Selective small antigenic structures are capable of inducing widespread autoimmunity which closely mimics the humoral fine specificity of human SLE.
abstract: Recent data have suggested that autoantibodies in lupus can progress from simple immunity against a few antigenic structures to a complex response against multiple autoantigens. Our aim was to determine whether these diverse epitope patterns can indeed be generated by antigenic challenge with a single, small structure. Rabbits were immunized with either a 60 kDa Ro peptide commonly antigenic in human systemic lupus erythematosus (SLE) (Ro 274-289) or one which is rarely a humoral target (Ro 500-515). Rabbits immunized with the antigenic peptide (Ro 274-289) not only developed antibodies to multiple epitopes of 60 kDa Ro and La, as has been described, but also produced non-cross-reactive antibodies to the common spliceosomal proteins Sm B' and D1, and nRNP A and C. Rabbits immunized with the Ro 274-289 peptide also mount a progressive, diversified immune response to the sequential antigenic regions of these proteins (60 kDa Ro, Sm B' and D1, nRNP A and C), which is nearly identical to that seen in human SLE. Animals immunized with the nonantigenic peptide Ro 500-515 develop antibodies only to 60 kDa Ro. These results demonstrate that loss of tolerance to select single, small antigenic structures can begin a cascade which virtually recreates, at the epitope level, the humoral autoimmune specificity seen in human SLE.
authors.affiliation: Oklahoma Research Foundation, Oklahoma City, OK 73114, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: McClain
authors.forename: R H
authors.initials: RH
authors.lastname: Scofield
authors.forename: B T
authors.initials: BT
authors.lastname: Kurien
authors.forename: T F
authors.initials: TF
authors.lastname: Gross
authors.forename: J A
authors.initials: JA
authors.lastname: James
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens; D015551:Autoimmunity / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D023421:Models, Animal; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D020733:RNA, Small Cytoplasmic; D011817:Rabbits; D012261:Ribonucleoproteins / Q000737:chemistry / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D017381:Spliceosomes / Q000276:immunology*; D055517:snRNP Core Proteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen
chemical_list: D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D010446:Peptide Fragments; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human