Department of Laboratory Medicine


Immunology Division



HETEROPHILE ANTIBODIES


CLINICAL UTILITY:

Heterophile antibodies, (those which react with antigens not responsible for their production), occur in a number of diseases, including infectious mononucleosis (IM). However, the IM heterophile appears to be specific for that disease and is usually found by the 4th to 10th day of disease, and almost always by the 21st day. Highest titers occur in the second or third week, with the antibody persisting at least six weeks. Titers do not correlate with the severity of disease. Occasionally, the antibody is found in respiratory infections in patients who have had IM months or years previously. Since the symptoms of IM often are similar to those found in various other infectious conditions, such as influenza, hepatitis and rubella, the screen for IM heterophile antibodies is a helpful diagnostic tool. However, occasional false positives have been reported in patients with hepatitis A, hepatitis B, leukemia, lymphomas and pancreatic carcinoma. Confirmation of a positive Monospot screen can be made with the heterophile absorption test or with Epstein-Barr serologies done in the Virology Division.

Heterophile antibodies (but not the IM heterophile) occur in other conditions such as serum sickness, and in a small percentage of normal individuals.

METHOD DESCRIPTION:

The method used to test for the IM heterophile antibody is agglutination. Heterophile antibodies, which have the characteristic of agglutinating sheep and horse red blood cells, can be separated from one another by differential absorptions before adding cells. In the heterophile screen (Monospot), the IM heterophile is removed from serum by beef cell extract, but not by guinea pig kidney extract. Other heterophiles are removed by guinea pig extract, and may or may not be removed by beef. The serum sickness heterophile is removed by both. A positive result for IM heterophile (in the Monospot screen) is reported if the guinea pig is positive, and the beef is negative. In the heterophile absorption, a titered assay based on the same principles, the presumptive titer is the result of agglutination of the patient’s serum by sheep red blood cells without prior absorption (thus, all heterophiles present will be quantitated). For a positive IM heterophile, the titer of antibodies must be <1:56 on the presumptive, positive following absorption of the serum with guinea pig kidney extract (or no more than two titers less than the presumptive), and negative following beef absorption (or more than two titers lower than the guinea pig). The Monospot test provides similar information by a faster and more convenient test.

REFERENCE RANGE:

Heterophile Antibody: Presumptive >1:56; negative on guinea pig and beef absorptions.
Monospot: Negative.

SPECIMEN REQUIREMENTS:

0.5 ml serum. (Heterophile absorption can be performed on same aliquot as the screen.)