Immunization with a peptide of Sm B/B ' results in limited epitope spreading but not autoimmune disease

An experimental model of systemic lupus erythematosus has recently been des cribed in normal animals. We sought to confirm and extend this model, which involved immunization of normal rabbits and mice with a peptide of Sm B/B' , PPPGMRPP. This peptide is an early target of the immune response in anti- Sm-positive patients,vith lupus, The peptide was used in a multiple Ag pept ide format, with multiple copies of PPPGMRPP bound to an inert lysine backb one. New Zealand White rabbits and A/J and C57BL/10ScSn mouse strains were immunized with PPPGMRPP-MAP. Pepscan assays were used to determine the epit ope spreading of the anti-PPPGMRPP-MAP response to other octamers of SmB/B' following immunization. We obtained high titer anti-PPPGMRPP-MAP IgG respo nses in the New Zealand White rabbits and A/J mice. The rabbits immunized w ith PPPGMRPP-MAP showed varying degrees of epitope spreading, while the A/J mice showed no spreading. We observed no autoantibodies to dsDNA or other anti-nuclear autoantibodies in our animals by ELISA or immunofluorescence, although anti-nuclear autoantibodies were found by Western blotting in some of the rabbits. No evidence of clinical disease was seen in our normal ani mals. These data underline the difficulties often associated with the repro duction of animal models in different laboratories.