Cross-reaction of lupus Anti-dsDNA antibodies with protein translation factor EF-2

This report elucidates a new cross-reactive intracellular target of anti-ds DNA antibodies. Previous experiments have demonstrated that some anti-dsDNA antibodies penetrate cells grown in tissue culture and all inhibit in vitr o translation. Data implicate a crossreactive antigen directly involved in protein synthesis: elongation factor-2 (EF-2). EF-2 was identified by N-ter minal sequencing of a band identified with an antibody to the ribosomal pro tein S1 from Leuconostoc lactis in Western blot assay. Anti-DNA antibodies bind directly to purified EF-2 from bovine liver in dot blot assays. Anti-d sDNA antibodies were shown to inhibit in vitro translation. This inhibiting effect of anti-dsDNA antibodies was partially restored by EF-2 and abrogat ed by dsDNA, suggesting this cross-reactive specificity. These data demonst rate a cross-reaction between anti-dsDNA antibodies and EF-2 which may lead to cellular dysfunction, as evidenced by inhibition of protein synthesis, and provide a direct pathogenic role for cell penetrating anti-dsDNA antibo dies. (C) 2000 Academic Press.