Antiribosomal antibodies in SLE, infection, and following deliberate immunization

ARA occur in approximately 10% of randomly selected SLE patients but in up to 40% of patients with active disease. Anti-P antibodies appear to be a highly specific diagnostic marker for SLE since they are rarely detected in other multisystem autoimmune disorders. ARA are most frequently directed against the P proteins and the shared conserved C-terminus of the P proteins is immunodominant in almost all sera tested. Anti-P antibodies increase in titer in patients with active disease and have been reported to be detected more frequently in patients with severe behavioral disturbances. This may be particularly true of patients with affective disorders. The clinical utility of serological tests for anti-P in central nervous system lupus must await large, prospective studies. Other ARA antibodies have been detected in patients with SLE. These antibodies include anti-28S rRNA, anti-S10, and anti-L12. In all cases, the frequency with which these antibodies are detected is increased in sera containing anti-P. The P proteins and the 28S rRNA epitope play essential, but as yet undefined, roles in GTPase activity on the ribosome. The L12 protein is the mammalian homologue of the E. coli and yeast proteins known to bind to the 28S rRNA epitope. These findings indicate that some SLE patients produce autoantibodies against multiple components of a functionally related domain of the ribosome. This, in turn, supports the notion that the ribosome initiates and/or maintains autoantibody production. Despite the evidence supporting an antigen driven immune response, attempts to induce anti-P antibodies by immunization with autologous ribosomes in the autoimmune strain of mouse, MRL, have been unsuccessful. It therefore seems likely that the ribosomal components must be altered in some way to break tolerance or that other abnormalities of the immune system are necessary for autoantibody production. Immunization with foreign ribosomes induce anti-P autoantibodies in mice and in apparently normal humans infected with the hemoflaggelate, T. cruzi. The ability of the P proteins to break tolerance in these situations is, most likely, explained by the provision of a T cell epitope (the foreign P protein) together with the multivalency of the P proteins on the ribosome (which activate autoreactive B cells). We therefore propose (Fig. 5) a two-signal model for autoantibody production similar to that suggested for T-B collaboration in the normal immune response and also in the GVHD model of lupus.(ABSTRACT TRUNCATED AT 400 WORDS)