IgG antinuclear antibodies with cross-reactive rheumatoid factor activity.
To investigate whether IgG antinuclear antibodies have cross-reactive rheumatoid factor activity, monoclonal IgG antibodies to DNA and Sm from autoimmune MRL-lpr/lpr mice were assayed by ELISA for binding to IgG antigens. Of the nine anti-DNA and anti-Sm monoclonals tested, six showed significant binding to affinity-purified rabbit IgG (RIgG) and human IgG (HIgG). To confirm that cross-reactivities were due to a single antibody, immunoabsorption of a representative polyspecific monoclonal termed C11 (anti-DNA, anti-Sm) on either Sepharose-DNA or Sepharose-RIgG resulted in marked loss of activity to the three antigens DNA, Sm and RIgG compared with immunoabsorption on Sepharose-bovine serum albumin. The monomolecular nature of the cross-reacting antibody was also suggested by inhibition analysis of C11; DNA inhibited C11 binding to RIgG 64%, whereas Sm inhibited binding to RIgG 33%. Aggregated RIgG and HIgG, however, did not inhibit binding of C11 to DNA, Sm, or solid-phase RIgG, probably reflecting the low affinity of this antibody for fluid phase Ig. Together, these findings suggest that antinuclear autoantibodies of the IgG, as well as the IgM, class have polyspecific IgG binding activity and suggest that IgG antinuclear antibodies may emerge from rheumatoid factor responses.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D003429:Cross Reactions; D004247:DNA / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis*; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D004247:DNA; D012217:Rheumatoid Factor