Human Anti-Estrogen Receptor Antibodies: Assay, Characterization, and Age- and Sex-Related Differences*

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Abstract
A binding assay was developed to measure the estrogen receptor (ER)-binding activity in serum. The method employed immunoglobulin G (IgG) adsorption with protein Abearing Staphylococcus aureus cells before incubation with tritium- labeled ER. Specificity studies employing chromatographic and electrophoretic analyses suggested that an IgG antibody (Anti-ER) was responsible for the serum activity. Anti-ER was found in human, rat, and mouse serum and exhibited species cross-reactivity. The antibody recognized both the 8S and 5S forms of the ER. Anti-ER was measured in 262 individuals ranging in age from 1–85 yr. The antibody was detected in all serum samples examined, suggesting its natural occurrence. When the study group was divided into three arbitrary age groups (young, 1–13 yr; middle age, 13–51 yr; older, >51 yr), significant differences in levels of antibody were found, with highest levels in the young, followed by the elderly, and lowest levels in the middle years. An examination of sex- as well as age-related differences in the population revealed a striking sex difference. Thus, the young male population had a lower level of antibody than the corresponding female population, and these levels in males declined throughout life to reach their lowest point in old age, whereas the high levels in young females declined in middle years and then increased significantly in the elderly. We postulate that the antibody is a subgroup of IgG of multifactorial etiology. The idiotypic network theory offers an explanation for the occurrence of these antibodies in normal serum, whereas an autoimmune mechanism could account for the secondary rise of anti-ER in the aging female population.