Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization.

Abstract A serum pool from 800 healthy donors and individual samples from three healthy donors were passed through tubulin, actin, thyroglobulin, myoglobin, fetuin, transferrin, albumin, cytochrome c, and collagen immunoadsorbent columns. Proteins were eluted from all the immunoadsorbents and were found to be essentially composed of the three major Ig classes and albumin. Isolated Ig fractions were studied by competitive and noncompetitive enzyme immunoassays and were shown to bind specifically to the antigens via their Fab fragment. When the isolated antibodies were tested by a noncompetitive assay, anti-tubulin antibodies were found to bind exclusively to tubulin, whereas the others bound mainly to their respective homologous antigens and to a lesser extent to one or more other antigens. When the isolated antibodies were examined by a competitive assay, they fell into three groups: The first group, consisting of anti-tubulin and anti-thyroglobulin, was only inhibited by their respective antigens. The second group was comprised of anti-actin, anti-myoglobin, and anti-fetuin; antibodies mainly inhibited by their respective antigens, but also to a significant degree by two or three additional antigens; thus, the reaction between anti-actin antibodies and immobilized actin was chiefly inhibited by actin, but tubulin and thyroglobulin also inhibited to some extent. The third antibody group consisted of anti-albumin, anti-transferrin, anti-collagen, and anti-cytochrome c, which bound specifically to the antigens but were only inhibited slightly or not at all by their respective antigens. Finally, immunocytologic staining showed antibody binding to constituents present in normal human cells. These results strongly suggest that natural antibodies against the nine antigens examined are present in normal human serum, and indicate that natural antibodies directed against a great variety of antigens—often self antigens—might be present in normal serum.