Heterophile antibodies are a type of antibody that can complicate diagnostic laboratory tests. Present in some individuals, they can lead to inaccurate test results, influencing medical decisions. Understanding their nature and impact is important for correct diagnoses and appropriate treatment.
What Defines Heterophile Antibodies
Heterophile antibodies are produced in response to external antigens broadly shared across species. Exposure to animal antigens (e.g., from pets, food, vaccines) can induce their formation.
They are characterized by their “polyspecific” nature, meaning they can bind to a variety of different antigens, frequently with weak affinity. This broad reactivity distinguishes them from the highly specific antibodies the immune system typically produces against a single pathogen or substance.
These antibodies are often of the IgM class, though other immunoglobulin types can also exhibit heterophile activity. An estimated 0.17% to 40% of the general population may have heterophile antibodies. They can be found in healthy individuals, sometimes arising naturally without a clear external trigger, and their production has also been linked to autoimmune or inflammatory conditions.
How They Impact Medical Tests
Heterophile antibodies primarily interfere with clinical immunoassays, which are laboratory tests that measure substances using antibodies. Many immunoassays, particularly “sandwich” assays, employ antibodies derived from animals, often mice, as part of their detection system.
Heterophile antibodies in a patient’s sample can bind non-specifically to these animal-derived reagents, creating a “bridge” between the capture and detection antibodies in the test. This non-specific binding can lead to erroneous results, either by falsely elevating a measured value (false positive) or, less commonly, by falsely lowering it (false negative).
For instance, in a sandwich immunoassay, if heterophile antibodies connect the assay’s antibodies in the absence of the target substance, it can mimic the presence of that substance, producing a false positive signal. Such inaccurate results can lead to unnecessary investigations, inappropriate treatments, or missed diagnoses.
Common Tests Susceptible to Interference
A wide range of medical tests are susceptible to interference from heterophile antibodies, particularly those that rely on immunoassay technology. These include tests for various hormones, tumor markers, and cardiac injury markers.
For example, thyroid function tests, measuring hormones like TSH, free T4, and free T3, can yield misleading results, potentially leading to incorrect diagnoses of hypothyroidism or hyperthyroidism and subsequent inappropriate treatment. Cardiac markers, such as troponin I, are also frequently affected, with heterophile antibodies causing falsely elevated levels that might suggest a heart attack in patients who have not experienced one. Similarly, tumor markers like human chorionic gonadotropin (hCG), prostate-specific antigen (PSA), and calcitonin can show false elevations, sometimes leading to misdiagnoses of malignancy or unnecessary surgical procedures and chemotherapy. Reproductive hormones (FSH, LH) and certain infectious disease markers can also be impacted.
Strategies to Identify and Minimize Interference
Laboratories and healthcare professionals employ several strategies to identify and minimize heterophile antibody interference. One common approach involves retesting the sample using an alternative immunoassay platform, as different assays may have varying susceptibilities to these antibodies.
Diluting the sample and observing if the results change non-linearly can also indicate interference, although this method is not always definitive. Blocking agents, such as Heterophile Blocking Tubes (HBT), are often used to neutralize or inhibit the interfering antibodies in a sample.
Clinical correlation remains a crucial step; if laboratory results do not align with a patient’s symptoms or clinical presentation, the possibility of heterophile antibody interference should be considered. Correlating test results with the patient’s overall medical picture helps ensure potential interferences are flagged, preventing misdiagnosis and guiding appropriate management.