Autoantibodies to the Ro/SSA antigen are conformation dependent. I: Anti-60 kD antibodies are mainly directed to the native protein; anti-52 kD antibodies are mainly directed to the denatured protein.
Recent studies have shown that Ro/SSA autoantigen is heterogeneous and the autoanti-Ro/SSA response is correspondingly heterogeneous. There are two isoform families; the 60 kD forms and the 52 kD forms. We studied the antigenic difference between the native and denatured Ro/SSA isoforms and found that the autoanti-Ro/SSA response to the native 60 kD antigen is quite homogeneous. All anti-Ro/SSA sera recognize the native kD antigen regardless of the reactivities to the 60 kD band on the Western blot. Surprisingly, no anti-Ro/SSA sera without anti-La/SSB reacts with the native 52 kD Ro/SSA, although sera with both precipitating anti-Ro/SSA and anti-La/SSB can immunoprecipitate the native 52 kD antigen. Anti-Ro/SSA sera exist which react exclusively with the native 60 kD Ro/SSA protein (10/43, 23%) while no anti-Ro/SSA sera have been found which react exclusively with the denatured 52 kD Ro/SSA antigen. In sera with anti-Ro/SSA precipitins alone, only antibody to the denatured 52 kD Ro/SSA molecule is found! In sera with anti-Ro/SSA and anti-U1 RNP precipitins, no antibody to either native or denatured 52 kD Ro/SSA is found, while in sera with both anti-Ro/SSA and anti-La/SSB precipitins, antibodies to both the native and denatured forms of 52 kD Ro/SSA are present. These data suggest that the anti-Ro/SSA response to the 60 kD molecule is driven by the native 60 kD Ro/SSA molecule while the molecular identification of the antigen drive in the anti-52 kD Ro/SSA response is unknown.
Itoh
Y
Y
Department of Medicine, College of Medicine, Oklahoma University Health Sciences Center, Oklahoma City 73104.
Reichlin
M
M
D000974:Antibodies, Antinuclear / Q000097:blood; D000918:Antibody Specificity; D001324:Autoantigens / Q000737:chemistry; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D037282:Calreticulin; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008970:Molecular Weight; D011487:Protein Conformation; D011489:Protein Denaturation; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D012859:Sjogren's Syndrome / Q000276:immunology; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D000939:Epitopes; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human; C035356:SS-A antibodies