Thus, the interference is not limited to monoclonal antibody based assays. The presence of heterophile antibodies has a high specificity for infectious mononucleosis. In about 3% of tg measurements heterophile antibodies will interfere with the results of the test. The frequency of subjects with heterophile antibodies was significantly greater in the population of nondiabetic relatives 31222, 14. Evaluation of a novel dry latex preparation for demonstration. Pdf heterophile antibody interference led to unneeded. We have developed a multiplexed fluorescent microsphere immunoassay for the simultaneous quantification of 10 cytokines in only 75. Im sera were tested by a hemadsorption immunocapture test hit for the detection of heterophile antibodies of igm, iga, and ige classes. Heterophile antibody interference in a multiplexed.
These antibodies can be detected by rapid agglutination assays, but falsepositive results have occasionally. Heterophile antibodies interfere with immunoassays. Epsteinbarr virus ebv is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious mononucleosis in. However, some falsenegative results have been shown to be due to a delayed im heterophile antibody response. Heterophile definition and meaning collins english dictionary. Evaluation of 12 commercial tests for detection of epstein. Falsepositive result provided by rapid heterophile antibody. Beef erythrocyte hemolysins and agglutinating antibodies to horse, goat, and camel erythrocytes are also demonstrable in infectious mononucleosis. Frequent false positive beta human chorionic gonadotropin. Medical researchers have proposed that heterophilic antibodies bind.
Ebv infection induces the production of several antibody classes, of which heterophile antibodies are one others include antii, rheumatoid factor and ana. The heterophilic antibodies are not species specific, but can bind to a variety of animal antibodies. Meridian diagnostics, and an absorption test monospot. Heterophile definition of heterophile by medical dictionary. Heterophile antibodies ha and igm are elevated during gestation in nigerian women who are receiving antimalarials. Heterophile antibodies are the hallmark of an ebv infection. Pdf human heterophile antibodies may develop after infection or contact with animal tissues or animal serum products. Heterophile antibodies, mantiglobulins, immunoglobulins and. The patient presented with the symptoms of hypothyroidism, which did not fit the results of the blood. Study of seven analytes on two automated immunoassay analyzers margarette jane ellis author for correspondence. Heterophile antibodies, originally described by paul and bunnell, are present in 90% to 95% of ebv infections at some point during the illness. Heterophilic antibodies are common, naturally occurring antibodies with low affinities. Heterophile antibodies are of particular importance in clinical medicine for their use in detecting epsteinbarr virus the causative agent of infectious mononucleosis. A human antibody that reacts with proteins from another species.
Techniques for identifying heterophile antibody interference are assay specific. In their recent article, kaplan and levinson provide an interesting account of the distinction between weak multispecific heterophile antibodies and the highly avid and specific human antianimal e. Techniques for identifying heterophile antibody interference. The effect on analyte recognition probably results from steric inhibition of hcg binding to complexed antibody. The heterophile antibody test is a rapid test which detects infectious mononucleosis that is caused by the epstein barr virus ebv. A new, dried antigencoated latex preparation for the demonstration of infectious mononucleosis im heterophile antibody dryspot im kit. The three groups of heterophile antibodies are polyspecific antibodies, antiimmunoglobulin antibodies, and highspecificity highaffinity antibodies. We describe here a 22monthold child with heterophile antibodies reactive with bovine serum albumin. Prevalence of heterophilic antibody interference in eight. The combination of high ha titres and relatively low frequency of positive mantiglobulins with elevated igm, but normal igg and positive creactive protein, suggests that infections other than malaria may be responsible for the increase of these circulating antibodies. How to use the monospot and other heterophile antibody.
In their recent article, kaplan and levinson provide an interesting account of the distinction between weak multispecific heterophile antibodies and the highly avid and specific. Virion had a low sensitivity for ebna igg antibodies, whereas biotest was negative for early antigen ea igm and ea igg from the dilutions 1. We read with interest the report on heterophilic antibodies as a case of false positive interference in thyroidstimulating hormone tsh assays. Heterophile antibodies, originally described by paul and bunnell 7 as sheep erythrocyte agglutinins, are present in about 90% of cases at some point during the illness. These antibodies can be detected by rapid agglutination assays, but falsepositive results have occasionally been reported for several conditions, including leukemia, rubella, malaria, systemic lupus erythematosus, pancreatic carcinoma, viral hepatitis, and human immunodeficiency virus infection. More on heterophile and human antianimal antibodies.
The aim of this case report is to raise awareness of the interference of heterophile antibodies in free thyroxine immunoassay. Heterophile antibodies are antibodies induced by external antigens heterophile antigens some crossreact with selfantigens. Mar 01, 2005 techniques for identifying heterophile antibody interference are assay specific. In young adulthood, the test has high sensitivity and specificity in the diagnosis of the primary ebv infection. By adding the term specific to antibodies with clearly defined immunogens, the term hama or other haaa could. Understanding the nature and characteristics of these antibodies provides a format for better identifying and removing them.
The numerous groups of heterophile antigensof which the forssman antigens are the best studiedconstitute significant exceptions. However, in infants and children under the age of 4 years with primary ebv infection, heterophile antibody responses are often not detected. Clinical adam morton when lab tests lie heterophile. Heterophilic antibody interference in laboratory tests. Im heterophile antibody titers have been shown to persist in some cases for months and. Clinical adam morton when lab tests lie heterophile antibodies. The mononuclear spot test or monospot test, a form of the heterophile antibody test, is a rapid test for infectious mononucleosis due to epsteinbarr virus ebv. This is in contrast to strong human antianimal antibodies produced against welldefined antigens as a result of treatment with animal immunoglobulins kaplan and levinson, 1999. In association with clinical signs and symptoms, virusspecific serology and heterophile antibody tests are widely used in confirming. Study of seven analytes on two automated immunoassay analyzers margarette jane ellis author for. The war on heterophilic antibody interference article pdf available in clinical chemistry 511.
Heterophile igm, iga, and ige antibodies in infectious. Bunnell pb antibodies was ascertained by a differential absorption test. Heterophile antigens link the species hogoxhuman blood group a, cathorse, and doghogcathuman, whereas several heterophile groups link otherwise diverse microorganisms. Im sera were tested by a hemadsorption immunocapture test hit for the detection of heterophile antibodies of igm, iga, and. Heterophile antigen accessscience from mcgrawhill education. After they observed that individuals with the infectious mononucleosis im made antibodies the heterophil antibodies that were possible to agglutinate sheep rbcs. Heterophilic antibodies detected with a murine antibody. The patient presented with the symptoms of hypothyroidism, which did not fit the results of the blood tests.
Heterophile antibodies segregate in families and are. The test is specific for heterophile antibodies produced by the human immune system in response to ebv. The iga deficient sera were also tested for igg antigoat and antimouse heterophile antibodies. Heterophile antibodies are a wellrecognized cause of erroneous results in immunoassays. In fact, heterophile antibodies have been referred to as preexisting hamas.
Test results for heterophile antibodies were not validated for sera belonging to this group. The three groups of heterophile antibodies are polyspecific antibodies, antiimmunoglobulin antibodies, and highspecificity highaffinity antibodies against antigens from animal species. Heterophile antigens link the species hogoxhuman blood. By adding the term specific to antibodies with clearly defined immunogens, the term hama or other haaa could continue to be used to refer to a heterophile antibody recognized in mouse assays or other animalspecific assays. When is a heterophile antibody not a heterophile antibody. Heterophile definition of heterophile by merriamwebster.
Heterophile and immunizationinduced antibodies against the free andor total hormone assay antibodies are known to cause falsely low or falsely high ft4 results 107, 108. These antibodies initiate weak interactions between antigens and antibodies, and may function to regulate the immune system. For example, in rheumatic fever, antibodies against group a streptococcal cell walls can also react with and thus damage human heart tissues. Fifty infectious mononucleosis im and 150 noninfectious mononucleosis non. In clinical practice, the most important significance of heterophile antibodies is their use in diagnosing infectious mononucleosis. Heterophilic antibodies are not a single, specific entity, but are. They can cause problems in immunoassays, particularly immunometric assays, where they can form a bridge between the capture and detection antibodies, leading to a falsepositive result in the absence of analyte or, if analyte is also present, to a false increase in measured concentrations. Antibodies abs are the fastest growing class of drugs and the reasons for this growth are obvious. Limited utility of serology and heterophile test in the. Heterophile antibodies to bovine and caprine proteins causing. Originally, the test was developed in 1932 by paul and bunnell. Ten microbiological departments in norway have participated in a multicenter evaluation of the following commercial tests for detection of epsteinbarr virus ebvspecific and heterophile antibodies. While modern immunoassays provide sensitive and specific means for the quantitation of cytokines in biological fluids, heterophile antibodies are still a wellrecognized cause of interference in the measurement of cytokines in these assays. Interference from heterophilic antibodies in tsh assays d j.
The spectrum of illness ranges from infectious mononucleosis im to posttransplant lymphoproliferative disorder ptld. Recombinant dna technology can be utilized to engineer improved binding or effector functions. Usually different species have different antigen sets. Heterophile antibody an overview sciencedirect topics. Tg heterophile antibodies interference very technical. A problem for all immunoassays article pdf available in clinical chemistry 341. The occurrence, direction falsely high or low, and degree of interference all depend on the formulation, including the type of antibody, of a given free hormone assay. May 23, 2018 the heterophile antibody test is actually red cells which detect cell antibodies formed as part of the polyclonal antibody response that occurs during an ebv infection. The specificity of heterophile antibodies in patients and healthy donors with no or minimal signs of infectious mononucleosis. They can cause problems in immunoassays, particularly immunometric assays, where they can form a bridge. Heterophile antibodies are antibodies produced against poorly defined antigens, and these are generally weak antibodies with multispecific activities. Heterophile definition is of, relating to, or being an antibody circulating in blood serum that is reactive with antigen originating in a different species.
While modern immunoassays provide sensitive and specific means for the quantitation of cytokines in biological fluids, heterophile antibodies are still a wellrecognized cause of interference in. Heterophile antigens are antigens of similar nature, if not identical, that are present in different tissues in different biological species, classes or kingdoms. Both thyroxine ft4 and thyroidstimulating hormone tsh were shown to be raised. The interference is probably mediated via the fc region of the antibodies used in the assay. Heterophilic antibodies are human antibodies that can bind animal antibodies.
Usually different species have different antigen sets but the hetereophile antigen is shared by different species. Ten microbiological departments in norway have participated in a multicenter evaluation of the following commercial tests for detection of epsteinbarr virus ebvspecific and heterophile. The combination of high ha titres and relatively low frequency. Epsteinbarr virus ebv infection is associated with significant morbidity and mortality in renal transplant rt recipients.
They have high specificity for their targets and are well tolerated. Heterophile antigen definition of heterophile antigen by. Heterophil antibody test definition of heterophil antibody. Heterophile antibodies definition of heterophile antibodies. Epsteinbarr virus ebv is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious mononucleosis in adolescents. Heterophile antibody tests, including the monospot test, are red cell or latex agglutination assays, which detect antired cell antibodies produced as part of a polyclonal antibody response. We verified that antibodybinding substances in serum that interfere in twosite immunoassays involving murine antibodies are heterophilic antibodies. Captia select viral capsid antigen vcamgebna centocor inc. The interference of heterophile antibodies in free thyroxine.
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