Serum antiguanosine antibodies as a marker for SLE disease activity and pathogen potential.
BACKGROUND
This article reviews research conducted on the immunogenicity of the nucleosides of DNA, especially guanosine, the most immunologically active nucleoside. Discussed is the relationship between circulating antibodies to guanosine, their potential role in SLE disease activity, the binding properties of monoclonal antiguanosine antibody (4H2) compared to polyclonal antiguanosine antibodies in humans with SLE, cell membrane penetration by these antibodies and their interference with signal transduction possibly related to their binding to mitochondria and their apparent GTPase activity.


METHODS
Enzyme-linked immunosorbent assay methodology was used to show clinical relationships between antiguanosine antibody levels and disease activity in SLE. These results are discussed along with methods of detecting cell penetration by this antibody using special staining techniques, laser-scanning microscope detection of mitochondrial localization, and interference of cAMP and pKA production/activation. Additionally, there is some discussion regarding the assay used to detect enzymatic activity of antiguanosine antibodies.


RESULTS
Enhanced circulating levels of antiguanosine antibodies in patients with SLE correlate closely with SLE disease activity. Other factors are discussed that support the pathogenic potential of these antibodies, including their ability to penetrate lymphocytes, bind to mitochondria, inactivate mitochondrial function, interfere with signal transduction, and their potential enzymatically activity.


CONCLUSIONS
Antiguanosine antibodies correlate with SLE disease activity and may be pathogenically important in SLE by interfering with signal transduction, inactivating mitochondrial and cell function in patients with SLE.
JL Pettis Memorial Veterans Medical Center, Research Service-151, K.K. Colburn M.D. Chief of Rheumatology, L.M. Green Ph.D. Molecular Immunologist, 11201 Benton Street Loma Linda, CA 92357, USA. Keith.Colburn@med.va.gov
Keith K
KK
Colburn
Lora M
LM
Green
D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002463:Cell Membrane Permeability; D006151:Guanosine / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism
D000906:Antibodies; D015415:Biomarkers; D006151:Guanosine