Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder of unknown etiology that is characterized by antibodies binding ribonucleoprotein complexes. The epitopes of SLE associated 60 kd Ro (or SSA) autoantigen share sequence with vesicular stomatitis virus (VSV) nucleocapsid (N) protein and SLE patients with anti-Ro are more likely to bind the N-protein than anti-Ro negative patients.
Method: We immunized New Zealand white (NZW) rabbits with purified VSV N-protein to examine the relationship between the immune response to N-protein and anti-Ro.
Results: After multiple immunizations with VSV N-protein, NZW rabbits produced not only IgG antibodies to VSV N-protein but also an autoimmune response to Ro antigen. The IgG fraction of the rabbit immune serum precipitates 60 kd Ro protein as well as its associated Y RNAs. Antibodies elicited by 10 immunizations of VSV N-protein bind to at least 20 linear epitope groups on VSV N-protein and over 25 linear epitope groups on 60 kd Ro protein. These antibodies also bound 5 of the 6 shared sequences between 60 kd Ro protein and VSV N-protein.
Conclusions: Our data demonstrate that an immune response initiated towards a foreign antigen, selected on the basis of sharing short sequence similarity with the autoantigenic epitopes of an autoantigen, can lead to an autoimmune response.