Antiguanosine antibodies in murine and human lupus have the internal image of G-binding proteins

• Published in: Journal of rheumatology Vol. 30; no. 5; pp. 993 - 997
• Main Authors: COLBURN, Keith K, WONG, Andrew L, WEISBART, Richard H, GREEN, Lora M
• Format: Journal Article
• Language: English
• Published: Toronto, ON The Journal of Rheumatology 01-05-2003; Journal of Rheumatology Publishing
• Subjects: Adolescent; Adult; Aged; Animals; Antibodies, Monoclonal - immunology; Antibody Specificity; Autoantibodies - analysis; Autoantibodies - immunology; Biological and medical sciences; Female; GTP-Binding Proteins - immunology; Guanosine - chemistry; Guanosine - immunology; Humans; Immunodominant Epitopes - immunology; Immunoglobulin G - analysis; Immunoglobulin G - immunology; Lupus Erythematosus, Systemic - immunology; Male; Medical sciences; Mice; Middle Aged; Protein Binding - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Human; Immunopathology; Connective tissue disease; Skin disease; Antigenic determinant; Antibody; Pathogenesis; Guanosine; Rodentia; Autoantibody; Autoimmune disease; Vertebrata; Specificity; Mammalia; Mouse; Animal; Systemic disease; Lupus erythematosus; Serum; Disseminated; ELISA assay; Comparative study; G protein; ANTIGUANOSINE SYSTEMIC LUPUS ERYTHEMATOSUS AUTOANTIBODIES G-PROTEINS
• ISSN: 0315-162X; 1499-2752

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. CONCLUSION: 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.