Anti-Estrogen Antibodies in Systemic Lupus Erythematosus: A Quantitative Evaluation of Serum Levels

Abstract

We measured the beta-estradiol binding capacity of serum gammaglobulins in four subject groups; 1) normal men, 2) normal women who had never taken oral contraceptives, 3) normal women who had a history of oral contraceptive use and, 4) patients with systemic lupus erythematosus (SLE). We used dextran-coated charcoal to strip endogenous estradiol from serum proteins, added ³H-estradiol, and measured its association with proteins in various electrophoretic fractions following zone separation on agarose gels. Most of the bound radioactivity was present in the albumin, beta and gammaglobulin fractions. Binding to gamma-globulins was elevated in SLE patients, and normal controls who had taken oral contraceptives, as opposed to other controls (p < 0.005). Gamma-region radioactivity could be removed by protein-G adsorption prior to zone electrophoresis. Isoelectric focusing revealed a pattern of tritiated-E₂ binding consistent with polyclonal B-cell activation in all groups. There was no correlation between the extent of gamma-region binding and the total serum immunoglobulin level for any of the groups studied, nor was there a correlation between E₂ binding and anti-DNA titers in the SLE group. The average anti-estradiol antibody concentration in SLE sera (assuming equimolar binding) was 105 ng/ml (95% CL = 92–118), whereas their average anti-DNA antibody concentration was in the ug/ml range. Thus, quantitatively, the level of anti-estradiol antibodies is at least an order of magnitude lower than the anti-DNA antibodies characteristic of this disease.