A heterophile antibody is an antibody produced by the human immune system that can react with antigens from different species. This phenomenon, known as cross-reactivity, occurs when the antibody binds to a substance other than the one that initially triggered its production. Their broad reactivity can have implications in diagnostic testing.
What Defines a Heterophile Antibody?
Heterophile antibodies possess distinct features. They often arise naturally in the body, or their production can be stimulated by infections, such as those caused by the Epstein-Barr virus, or by environmental exposures. A defining characteristic is their ability to bind to antigens from unrelated animal species, even though they were generated in humans. For example, a human heterophile antibody might react with proteins found in animal blood cells.
These antibodies exhibit low affinity for their targets, meaning they do not bind as strongly as specific antibodies. They also demonstrate broad specificity, allowing them to react with a wider range of antigens. Compared to antibodies that precisely target a single pathogen or substance, heterophile antibodies can interact with multiple, often poorly defined, external antigens.
How Heterophile Antibodies Impact Diagnostic Tests
The presence of heterophile antibodies can affect the accuracy of various laboratory diagnostic tests. Their non-specific binding can lead to results that do not align with a patient’s clinical presentation, causing either false positive or false negative outcomes. This interference occurs because heterophile antibodies can bind to reagents or other components within the test system, rather than to the target substance being measured.
Many diagnostic tests, especially “sandwich” immunoassays, are susceptible to this interference. In these assays, heterophile antibodies can bridge the capture and signal antibodies used in the test, creating a false signal even when the actual antigen is not present. This unintended binding can lead to an incorrect measurement of hormones, tumor markers, or other substances, misguiding diagnosis and treatment.
Specific Instances: Heterophile Antibodies in Disease Detection
Heterophile antibodies are relevant in the diagnosis of infectious mononucleosis, an infection caused by the Epstein-Barr Virus (EBV). The Monospot test, a rapid diagnostic tool, detects these antibodies produced in response to EBV infection. These IgM antibodies show an affinity for sheep and horse red blood cells, which is the basis of the test. They appear within the first week of symptoms and become undetectable within three to six months.
Beyond infectious mononucleosis, heterophile antibodies can also interfere with other diagnostic assays. They cause issues in tests for certain tumor markers, hormone levels (such as thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone), and drug levels. For example, they can lead to falsely low serum cortisol levels, potentially resulting in an incorrect diagnosis.
Addressing Heterophile Antibodies in Laboratory Testing
Laboratories employ several strategies to identify and mitigate the interference caused by heterophile antibodies to ensure accurate diagnostic results. One common approach involves using blocking agents, such as non-immune animal serum, which can bind to the heterophile antibodies and prevent them from interfering with the test. Some samples may also undergo pre-treatment to neutralize these interfering antibodies.
Another method involves performing serial dilutions of the patient’s sample; if the result does not dilute proportionally, it suggests interference. Laboratories may also utilize alternative testing methods that are less susceptible to heterophile antibody interference. Recognizing the potential presence of these antibodies allows for appropriate measures to be taken, contributing to more reliable patient diagnoses.