When Is a Heterophile Antibody Not a Heterophile Antibody? When It Is an Antibody against a Specific Immunogen

Abstract

Heterophile antibodies are antibodies produced against poorly defined antigens. These are generally weak antibodies with multispecific activities. Human anti-animal antibodies that develop as a result of treatments with animal immunoglobulins are antibodies with strong avidities, produced against well-defined antigens. Although heterophile antibodies and human anti-animal antibodies interfere with immunological assays by similar mechanisms, modes for identifying the sources of the antibodies and for circumventing or retarding the interference may differ. Unfortunately, there has not been a well-organized attempt to encourage correct definition of these antibodies. This problem of inexact definition is highlighted by recent articles in this Journal. In the present discussion, we examine the history leading to this problem and discuss the origins and the reasons that the nature of the antibody is important for rectifying the problem. We propose a simple nomenclature for general usage that should appropriately characterize these antibodies in most cases.

Venous Thromboembolism or Vermin?

“…tory of treatment with injected animal immunoglobulins, but reported that as a child, she had kept a pet rabbit, guinea pig, and hamster and spent time with pet mice. Her interfering antibody could be a specific HAAA arising from vermin exposure, or a heterophile antibody, either capable of reacting with vermin (mouse monoclonal antibodies) in the assay (1,3,10). In cases of animal handling, if the interfering antibody shows a preference for the same species as the suspected immunizing species, it should be termed a specific HAAA (10).…”

“…Her interfering antibody could be a specific HAAA arising from vermin exposure, or a heterophile antibody, either capable of reacting with vermin (mouse monoclonal antibodies) in the assay (1,3,10). In cases of animal handling, if the interfering antibody shows a preference for the same species as the suspected immunizing species, it should be termed a specific HAAA (10). If this was the case, we would expect it to be a specific human antimouse antibody that reacts with mouse monoclonal assay antibodies (1,10).…”

“…In cases of animal handling, if the interfering antibody shows a preference for the same species as the suspected immunizing species, it should be termed a specific HAAA (10). If this was the case, we would expect it to be a specific human antimouse antibody that reacts with mouse monoclonal assay antibodies (1,10). Comparing the original assay, which included a mouse heterophilic blocking reagent, with the first alternative assay that did not include a blocker, her antibody reacted in the original assay in spite of the presence of a blocker, but was unreactive in the latter, which had no blocking capacity; thus, the antibody does not seem to be specific for mouse antibodies (1).…”

Investigation of interference from canine anti‐mouse antibodies in hormone immunoassays

“…An alternative approach to tackle immunoassay interference is to deplete the samples of Igs by treating the samples with a precipitant, such as polyethylene glycol (PEG). PEG lowers the solubility of Igs and has been reported to precipitate both serum IgG and IgM efficiently . A sample treatment procedure with PEG is quickly performed, and feasible to implement into normal laboratory routines.…”

What should be done when thyroid function tests do not make sense?

“…Many manufacturers include panels of antigens or pre‐immune serum from source animals to ‘mop up’ HAAs. However, heterophile antibodies (which are weak polyspecific antibodies that are similarly capable of causing negative or positive interference) 11,12 can prove more difficult to remove. Such interference in the TSH assay can be seen in cases of Graves’ Disease and in patients with positive rheumatoid factor (RhF) 13 …”