heterophile

Heterophile antibodies are a class of antibodies capable of reacting with antigens that are not related to the original immunizing antigen or even to different species. In laboratory medicine, they are most famously described as cross-reactive antibodies that agglutinate red blood cells from animals such as sheep or horses. The antibodies are often polyreactive and can be present without a known exposure to the specific animal antigens.

Clinically, heterophile antibodies are associated with infectious mononucleosis (IM), typically due to infection with Epstein-Barr virus (EBV). In IM, the immune response can produce these cross-reactive antibodies, which can be detected by heterophile antibody tests such as the Monospot or the Paul-Bunnell test. A positive result supports the diagnosis of EBV-related IM in the appropriate clinical context, but it is not EBV-specific. False negatives can occur, especially early in illness or in young children, and EBV-specific serologies (for example, VCA IgM and EBNA IgG) provide more definitive confirmation.

Heterophile antibodies can also cause interference in immunoassays. Because they can react with animal antibodies used in diagnostic tests, they may yield false-positive or false-negative results in certain serologic or immunoassay platforms. Laboratories may employ blocking reagents or alternative assay designs to mitigate such interference.

In summary, heterophile antibodies are cross-reactive antibodies important in the serologic evaluation of infectious mononucleosis and in the broader context of laboratory assay interference, reflecting the diverse and polyreactive nature of the humoral immune response.