Immunoassays used for human in vitro diagnostics (IVD) often use animal-sourced antibodies to recognize specific disease markers. A small percentage of individuals, however, may have antibodies in their blood that could react with the animal antibodies in the diagnostic assay and thereby interfere with detection of the disease markers causing a false positive result. Such an interfering antibody is termed a heterophilic antibody (HA).
Due to the wide use of mouse monoclonal antibodies in diagnostic applications, the most well-known HA interference is a result of HAMA (human antimouse antibodies). Rheumatoid factor (RF), an autoantibody that reacts with the patient’s own immunoglobulin (Ig), may also cross-react with animal Ig resulting in RF interference, which is similar to HA/HAMA interference.
Much like HAMA, HA to other animals such as goat (HAGA), sheep (HASA), and rabbit (HARA) may cause false results, especially when antibodies originating from such animals are used in immunoassays.
Although the frequency of these interferences is low, the false positive results have a significant negative impact on the quality and competitiveness of diagnostic assays as well as on the lives of those individuals who have been falsely diagnosed.