Lupus Humoral Autoimmunity after Short Peptide Immunizationa

Anti-Sm is a common and specific autoantibody found in systemic lupus erythematosus.The peptide, PPPGMRPP, is found in Sm B/B' and is an early target of the autoimmune response in some anti-Sm precipitin-positive patient sera.' Rabbits and some strains of inbred mice develop anti-Sm autoantibodies with B cell epitope spreading of the autoimmune response after immunization with this peptide on an M A P backbone of branching lysines.*In addition to generating antibodies that bind PPPGMRPP and other spliceosomal peptides (as well as the Sm and nRNP proteins), these animals variably develop positive antinuclear antibodies (ANA), anti-doublestranded DNA antibodies (dsDNA), proteinuria, elevated creatinine, seizures, alopecia, and thrombocytopenia.Rabbits immunized with control protocols develop none of these features of lupus nor of autoimmunity.*This common antigenic target of Sm BIB', PPPGMRPP, is very similar to a region of the Epstein-Ban nuclear antigen-1 (EBNA-1) protein, PPPGRRP.We have previously reported that lupus patients, but not normals nor patients with other autoimmune diseases, have antibodies that bind this region of EBNA-1.'In addition, both the major autoantigenic target of Sm D in lupus and EBNA-1 have repeated glycine-arginine sequence^.^-^These glycine-arginine repeats of the EBNA-1 protein specifically bind human lupus sera.4~~' b o rabbits have been immunized, using a protocol previously published?with the PPPGRRP-MAP@' peptide of EBNA-1.Both rabbits mount an immune response to the peptide of immunization (FIGURE 1, panel A).In addition, early in the immunization protocol these rabbits both develop antibodies that cross-react with the PPPGMRPP-MAP@' peptide of Sm B/B' (FIGURE 1, panel B).Neither of these animals have antibodies that bind any of three different Ro/SSA-MAP peptides.