Dual binding capabilities of anti-double-stranded DNA antibodies and anti-ribosomal phosphoprotein (P) antibodies.

The aim of this study is to identify distinctive properties of pathogenic anti-double stranded DNA antibodies and anti-ribosomal P antibodies. The binding activity of anti-dsDNA and anti-ribosomal P antibodies to their cognate antigens in 0.15 M and 1.5 M NaCl solutions on ELISA was examined. All anti-dsDNA and anti-ribosomal P antibodies exhibited a loss of their binding activity from 37.5 to 100% and from 2.3 to 97.4% in high ionic strength buffers, respectively. In contrast, anti-U1RNP antibodies and anti-Ro/SSA antibodies lost from 0 to 32.7% and from 0 to 40.1% of their binding activity, respectively. Anti-dsDNA and anti-ribosomal P antibodies from patients with nephropathy showed significantly higher binding activity in high ionic strength buffers than those from patients without nephropathy. Study of paired sera from lupus nephritis patients revealed that anti-dsDNA and anti-ribosomal P antibodies from patients during disease flare show stronger binding activity in high ionic strength buffer than those during remission. Most anti-dsDNA and anti-ribosomal P antibodies bind their antigens by ionic interactions that are sensitive to high salt. Such dual binding capability of anti-dsDNA and anti-ribosomal P antibodies may underlie their multiple cross reactivities to various epitopes and help elucidate the pathogenic potential of autoantibody subsets.

Further characterization of the autoantibody response of Palmerston North mice.

PN mice spontaneously develop, with age, a lupus-like disease. The present study further evaluated autoantibody production in female PN mice. As early as 1 month of age, all PN mice had detectable IgM antibodies to dsDNA and ssDNA and two-thirds produced IgM anticardiolipin antibodies. By 3 months of age, all PN mice exhibited evidence of isotype switch in their autoantibody response; 88-100% had serum IgG antibodies to ssDNA and dsDNA, respectively. By 6-12 months of age, essentially all female PN mice had IgG antibodies to ssDNA, dsDNA, cardiolipin and other phospholipids (PS, PC, PI, and PG), and IgG and 63% produced IgG anti-mouse erythrocyte antibodies. In addition, 50-100% produced IgA antibodies to dsDNA and ssDNA, and one-third produced IgA anti-IgG antibodies. Antibodies to U1RNP and Sm were present in 81% of 6- to 12-month-old PN mice and 39-94% had IgG or IgM antibodies to mouse thymocytes. Although all four IgG isotypes were represented in the anti-dsDNA response, IgG1 antibodies dominated the IgG anticardiolipin response. The presence of IgA autoantibodies and the predominance of IgG1 in the IgG anticardiolipin response suggest that IL-4 and either IL-5 and/or TGF-beta serve as B cell stimulatory cytokines for autoreactive B cells in PN mice.