Antiguanosine antibodies in murine and human lupus have the internal image of G-binding proteins.
OBJECTIVE
To examine the binding specificities of serum IgG antibodies of mouse and human origin directed against guanosine. The immunodominance of guanosine compared with the other nucleosides was established in the MRL/lpr murine model of systemic lupus erythematosus (SLE). Serum antiguanosine autoantibodies in human lupus correlate with nephritis and polyserositis in acute disease as well as in exacerbations of disease symptoms.


METHODS
Antiguanosine autoantibodies obtained from humans with SLE were compared to a murine monoclonal antiguanosine antibody, 4H2. The fine specificity of the antiguanosine-binding site was determined by methylation of specific positions on the guanosine molecule and using defined analogs in competitive ELISA.


RESULTS
Competitive inhibition assays revealed that serum antiguanosine antibodies bind across the 1 and 7 positions of the guanosine molecule (p < 0.01) and that an oxygen is necessary at position 6 in the molecule. 4H2 exhibited the same binding specificity for guanosine as human polyclonal antiguanosine antibodies, showing a conserved epitope across species. When the fine specificity was compared with known epitopes, the antiguanosine antibodies were found to have the internal image of a G-binding protein, identical to that of the Ha-ras oncogene product p21.


CONCLUSIONS
The finding that antiguanosine autoantibodies vary directly with specific features of SLE, especially nephritis and polyserositis, suggests that they may contribute to the pathology of SLE. Our findings that antiguanosine antibodies have G-binding protein active site homology support the possibility that this species of antibody might interfere with cell signal transduction.
Colburn
Keith K
KK
J.L. Pettis Memorial Veterans Medical Center, Loma Linda University Medical School, Loma Linda, California, USA. Kieth.Colburn@med.va.gov
Wong
Andrew L
AL
Weisbart
Richard H
RH
Green
Lora M
LM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D006151:Guanosine / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D006151:Guanosine; D019204:GTP-Binding Proteins