Humoral antigenic targets of the ribosomal P0 lupus autoantigen are not limited to the carboxyl region

Autoantibodies binding the ribosomal P phosphoproteins are highly specific for systemic lupus erythematosus (SLE) and can be found in precipitating levels in approximately 15% of these patients. Anti-ribosomal P antibodies are directed against three proteins, and the primary autoimmune target of this response has been described as a common 22-amino acid sequence. Sera from 31 anti-ribosomal P immunodiffusion-positive SLE patients were tested for C-terminal P-peptide reactivity by ELISA. Sera from three patients (9.7%) were negative for the peptide ELISA, despite having anti-ribosomal P by immunodiffusion and Western blot. In addition, inhibition experiments showed that the common P-peptide response accounts for a variable amount of anti-ribosomal PO reactivity (52-89% of the response dependent upon the patient serum). Based upon these findings, fine-specificity sequential humoral epitope mapping of ribosomal PO was performed. Several common sequential antigenic targets were defined dispersed throughout the molecule. The most commonly targeted epitopes included RDMLLANKV-PAAARA (amino acids 99-113, 11 of 12 patients reactive) and QALGITT-KISRGT (amino acids 139-151, 9 of 12 patients reactive). This study confirms that the P22 ribosomal peptide is commonly targeted in SLE and accounts for a variable percentage of the anti-ribosomal P response. Additional anti-ribosomal P humoral epitopes are described.