Heterophilic antibodies: a problem for all immunoassays.

TLDR

Serum heterophilic antibodies form soluble immune complexes with murine anti‑hCG antibodies. Heterophilic antibodies reduce recognition of hCG by the reagent antibody. Approximately 30 % of samples containing heterophilic antibodies falsely show elevated hCG, likely due to steric inhibition, and these antibodies also bind immunoglobulins from several species.

Abstract

We verified that antibody-binding substances in serum that interfere in two-site immunoassays involving murine antibodies are heterophilic antibodies. Incubation of serum containing heterophilic antibodies and a murine monoclonal antibody to human choriogonadotropin (hCG) leads to formation of a series of soluble immune complexes. We investigated the recognition of hCG by reagent antibody in the presence of heterophilic antibodies and found this recognition to be diminished. Consequently, about 30% of serum samples containing heterophilic antibodies falsely appear to contain increased concentrations of hCG. The effect on analyte recognition probably results from steric inhibition of hCG binding to complexed antibody. Heterophilic antibodies detected with a murine antibody also bound immunoglobulin from several other species but did not bind all of those tested.