Preferential adsorption of cationic anti-DNA antibodies with immobilized polyanionic compounds, dextran sulfate.
It has been shown that cationic anti-DNA antibodies have nephritogenic potential in murine models of lupus nephritis. More recently, we have reported that there is a close relationship between the presence of circulating cationic anti-DNA antibodies and the development of lupus nephritis in humans, and that the cationic anti-DNA antibodies bind to heparan sulfate, a major glycosaminoglycan in glomerular basement membrane, much better than neutral anti-DNA antibodies. This suggests that cationic anti-DNA antibodies of the IgG class may be responsible for development of nephritis in vivo in patients with systemic lupus erythematosus. In this study, we first studied reactivity of anti-DNA antibodies with a panel of glycosaminoglycans in vitro using ELISA methods, and found that anti-DNA antibodies cross-react with dextran sulfate, hyaluronic acid and chrondroitin sulfate. The reactivity and selectivity of dextran sulfate with anti-DNA antibodies was confirmed by in vitro immunoadsorption of the patient's sera with dextran sulfate-fixed column; incubation of auto-antibody-positive sera with dextran sulfate cellulose column removed anti-DNA, but not anti-RNP, anti-Sm, anti-SSA and anti-SSB antibodies from the sera in vitro. Of note is that dextran sulfate cellulose column absorbed exclusively, if not all, cationic anti-DNA antibodies in their sera. Nonspecific binding of total immunoglobulins as well as total proteins to the column was marginal. It has been suggested that cationic anti-DNA antibodies in sera of patients with refractory lupus nephritis could be efficiently removed by apheresis using dextran sulfate column.
Suzuki
N
N
Division of Allergy and Rheumatic Diseases, St. Marianna University School of Medicine, Kanagawa, Japan.
Otuka
I
I
Harada
T
T
Mizushima
Y
Y
Sakane
T
T
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification; D016264:Dextran Sulfate / Q000737:chemistry*; D005260:Female; D006801:Humans; D007164:Immunosorbents / Q000737:chemistry*; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D012680:Sensitivity and Specificity
D000974:Antibodies, Antinuclear; D007164:Immunosorbents; D016264:Dextran Sulfate