The fine specificity of IgG antiguanosine antibodies in systemic lupus erythematosus.

The antigen specificity, isotype, and subclass of antinuclear antibodies may be related to their pathogenicity in systemic lupus erythematosus (SLE). Our laboratory found that IgG antibodies that bound the nucleoside, guanosine, occurred frequently in SLE patients. In contrast, sera from healthy subjects contained IgM but not IgG antiguanosine antibodies. The present studies were designed to characterized the fine specificity of IgG antiguanosine antibodies in SLE and compare them with IgM antiguanosine antibodies in normal sera. Serum antinuclear antibodies from six healthy subjects and six SLE patients were isolated by affinity binding to guanosine and measured by an enzyme-linked immunosorbent assay (ELISA). IgM in normal sera, and both IgM and IgG in SLE sera bound guanosine. IgM antiguanosine antibodies in normal sera were polyspecific and bound other nucleosides and 1-methylguanosine but not denatured DNA (ssDNA). In contrast, IgG antiguanosine antibodies from the SLE patients bound guanosine and ssDNA but not other nucleosides or 1-methylguanosine. SLE IgM antiguanosine antibodies had the same fine specificity and bound guanosine and ssDNA but not any of the other nucleosides. These results suggest that SLE IgG and IgM antiguanosine antibodies have fine specificity in contrast to the polyspecific IgM antibodies in normal sera. In addition, subclass analysis indicated that all SLE patients had either IgG1 or IgG3 subclass of antiguanosine antibodies that bind complement. Characterizing the isotype, subclass, and fine antigen specificity of antiguanosine antibodies should assist in evaluating their potential pathogenicity in SLE.

Antiguanosine antibodies: a new marker for procainamide-induced systemic lupus erythematosus.

Antinuclear antibodies are present in most patients receiving procainamide. To ascertain whether IgG antiguanosine antibodies are associated with the development of the symptoms of systemic lupus erythematosus, we compared the levels of these antibodies in the sera of 65 patients receiving procainamide: 18 with procainamide-induced symptoms and 47 asymptomatic patients. Antinuclear antibodies measured by immunofluorescence were present in the 18 patients with drug-induced symptoms but also in 24 asymptomatic patients. Similarly, elevated serum levels of antibodies to single-stranded DNA were found in 15 patients with symptoms and in 20 asymptomatic patients. In contrast, levels of IgG antiguanosine antibodies were elevated in 15 patients with drug-induced symptoms, but in only 3 asymptomatic patients. Antiguanosine antibodies binding to single-stranded DNA were found primarily in patients with arthritis, pleuritis, and pericarditis. These results suggest a strong association between IgG antiguanosine antibodies and major manifestations of procainamide-induced systemic lupus erythematosus.