Cross-reaction of lupus anti-dsDNA antibodies with protein translation factor EF-2.
This report elucidates a new cross-reactive intracellular target of anti-dsDNA antibodies. Previous experiments have demonstrated that some anti-dsDNA antibodies penetrate cells grown in tissue culture and all inhibit in vitro translation. Data implicate a cross-reactive antigen directly involved in protein synthesis: elongation factor-2 (EF-2). EF-2 was identified by N-terminal sequencing of a band identified with an antibody to the ribosomal protein 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-dsDNA antibodies were shown to inhibit in vitro translation. This inhibiting effect of anti-dsDNA antibodies was partially restored by EF-2 and abrogated by dsDNA, suggesting this cross-reactive specificity. These data demonstrate 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 antibodies.
Alberdi
F
F
Arthritis and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Dadone
J
J
Ryazanov
A
A
Isenberg
D A
DA
Ravirajan
C
C
Reichlin
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002417:Cattle; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008099:Liver / Q000737:chemistry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D020652:Peptide Elongation Factor 2 / Q000276:immunology* / Q000302:isolation & purification; D014176:Protein Biosynthesis / Q000187:drug effects / Q000276:immunology*; D011817:Rabbits; D012269:Ribosomal Proteins / Q000276:immunology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D007074:Immunoglobulin G; D020652:Peptide Elongation Factor 2; D012269:Ribosomal Proteins; C015494:ribosomal protein S1; D004247:DNA