Peptide mimicking antigenic and immunogenic epitope of double-stranded DNAin systemic lupus erythematosus

Autoantibodies to double-stranded (ds) DNA are an important diagnostic mark er and pathogenic factor for systemic lupus erythematosus (SLE), Identifyin g dsDNA mimotopes is a way to discover diagnostic and therapeutic candidate s for SLE, 'Mono-specific' SLE anti-dsDNA antibodies were obtained by affin ity purification using dsDNA-coupled Sepharose column. Using the anti-dsDNA antibodies to screen a phage peptide library, we were able to identify a m imotope that has a motif peptide sequence of RLTSSLRYNP. This chemically sy nthesized peptide could be recognized by 88% (37 out of 42) of anti-dsDNA a ntibody-positive SLE sera with a cut-off point at mean + 3 SD of the negati ve control sera at OD492. The reaction of the peptide with SLE sera in ELIS A was highly correlated with that of dsDNA (r = 0,809, P < 0,0001). Of part icular interest, not only dsDNA but also single-stranded (ss) DNA and nativ e RNA could inhibit the binding of the peptide with SLE sera, suggesting th at the mimotope is shared by ds and ssDNAs as well as native RNA, whereas d enatured RNA was not observed to inhibit the binding. The peptide was also able to elicit an immune response in rabbits and the anti-peptide rabbit se rum was observed to cross-react with the peptide, ss and dsDNAs, and ss and dsDNAs could inhibit the binding of the anti-peptide serum and the peptide . However, the inhibition was not obtained with RNA. Our findings demonstra te the potential of the peptide mimic in diagnostic tests of SLE, and in th e investigation of anti-DNA antibody origin and of DNA-anti-DNA antibody in teraction.