LUPUS HUMORAL AUTOIMMUNITY INDUCED IN A PRIMATE MODEL BY SHORT PEPTIDE IMMUNIZATION

Background: Systemic lupus erythematosus (SLE) is characterized by hum oral autoimmunity against the spliceosomal proteins, including Sm B/B' , In SLE patients with anti-Sm B/B' antibodies the proline rich sequen ce, PPPGMRPP, is the predominant Sm B/B' autoimmune epitope and appear s to be an early target in the development of the anti-Sm B/B' respons e. Methods: Two female baboons were immunized with the PPPGMRPP peptid e from the Sm B/B' spliceosomal protein constructed on a MAP(TM) backb one in Freund's adjuvant, One female control baboon was immunized with Freund's adjuvant alone, Baboon sera were collected and assessed for antibody binding to the spliceosomal proteins and compared to SLE pati ent and control sera. Results: Peptide immunized baboons developed ant ibodies to multiple regions of the Sm B/B' protein, as well as reactiv ity against other spliceosomal proteins, Consistent with serologic man ifestations found In SLE, experimental baboons also acquired anti-nucl ear antibodies, anti-nuclear ribonucleoprotein (nRNP) antibodies and, in one animal, anti-double stranded DNA antibodies, The control animal had none of these immunologic findings. Conclusions: Immunization wit h PPPGMRPP is capable of initiating a humoral autoimmune response in p rimates against the Sm, nRNP complex from which the peptide was derive d. The additional autoantibody specificities generated in experimental animals are similar to those found in human SLE sera, This study is t he first evidence of peptide induction of SLE humoral autoimmunity in a primate model.