Humoral Antigenic Targets of the Ribosomal P0 Lupus Autoantigen Are Not Limited to the Carboxyl Region

Abstract

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 P0 reactivity (52-89% of the response dependent upon the patient serum). Based upon these findings, fine-specificity sequential humoral epitope mapping of ribosomal P0 was performed. Several common sequential antigenic targets were defined dispersed throughout the molecule. The most commonly targeted epitopes included RDMLLANKVPAAARA (amino acids 99-113, 11 of 12 patients reactive) and QALGITTKISRGT (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.