Epitope patterns of Anti‐RNP antibodies in rheumatic diseases evidence for an antigen‐driven autoimmune response

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Abstract
Autoantibodies against small nuclear ribonucleo‐proteins (snRNP) are common in systemic lupus erythematosus and related disorders. The 3 categories, anti‐(U1)RNP, anti‐(U1,U2)RNP, and anti‐Sm, all contain a common antibody specificity directed against the U1 snRNP‐associated A protein. To determine the specificity of anti‐U1 snRNP A protein antibodies for various antigenic sites, we tested 26 different anti‐snRNP‐positive sera for reactivity with fragments of the U1 snRNP A protein, which was produced using recombinant DNA technology. Several different fragments were shown to contain autoimmune‐reactive epitopes, which indicates that the antibody response against the U1 snRNP A protein is polyclonal. Antibodies against a discontinuous or conformational epitope were found in most of the sera tested, regardless of whether they were classified as anti‐(U1)RNP, anti‐Sm, or anti‐(U1,U2) RNP. These results strongly support the hypothesis that the anti‐snRNP autoimmune response is antigen driven.