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Limitations of immunofluorescence tests in the diagnosis of infectious mononucleosis
Abstract:
The relative value of heterophil agglutinins (HA) and of specific EBV antibodies in the diagnosis of infectious mononucleosis (IM) was assessed in 108 cases of the disease and in 280 controls. Among the 108 cases 93 were HA-positive by sheep cells in at least one of their sera, while 15 were HA-negative by the same test. Among the 280 controls false-positive HA tests were not encountered except in eight cases with the horse cell microtitre tests. With one of the two slide tests at least two false-positive tests and 12 false-negative tests were also found but these sera had low titres in microtitre tests. The HA life-span was found to be unexpectedly long in a few cases, sheep cell HA lasting up to 8 to 10 months and horse cell HA up to 21 to 23 months.Many false-positive tests may therefore not be true false-positives and may result from the persistence of HA following unrecognized mononucleosis months before. Virtually all cases of IM had (or developed) antibodies to Epstein-Barr virus, viral capsid antigen (EBV-VCA), whereas only half of the controls were EBV-VCA-positive. The comparative analysis of nonspecific and specific test results in mononucleosis allows the following conclusions: (1) horse cell microtitre tests and the monospot test are more sensitive than sheep cell microtitre tests and the monotest; (2) false-negative results are occasionally seen with the latter tests but not with the former; (3) more false-positive results, however, are probably seen with the former tests; and (4) specific EBV-IgM and EBV-EA antibody tests are useful in the diagnosis of selected borderline cases of mononucleosis.
Insights
Diagnosing infectious mononucleosis (IM) involves comparing heterophil agglutinins (HA) and Epstein-Barr virus (EBV) antibodies. Specific EBV antibody tests are useful for borderline cases, while HA tests show varying sensitivity and false-positive rates.
Area of Science:
- Immunology
- Virology
- Clinical Diagnostics
Background:
- Infectious mononucleosis (IM) diagnosis relies on heterophil agglutinins (HA) and Epstein-Barr virus (EBV) antibodies.
- Assessing the diagnostic utility of different HA tests and EBV antibody detection is crucial for accurate IM diagnosis.
Purpose of the Study:
- To compare the diagnostic value of heterophil agglutinins (HA) and specific EBV antibodies in infectious mononucleosis (IM).
- To evaluate the sensitivity and specificity of various HA tests (sheep cell, horse cell, slide tests) and their comparison with EBV antibody detection.
Main Methods:
- Analyzed sera from 108 IM cases and 280 controls using sheep cell microtitre, horse cell microtitre, and slide tests for HA.
- Detected Epstein-Barr virus viral capsid antigen (EBV-VCA) antibodies in cases and controls.
- Investigated the persistence of HA in a subset of individuals.
Main Results:
- Horse cell microtitre and Monospot tests demonstrated higher sensitivity for IM diagnosis compared to sheep cell microtitre and Monotest.
- False-negative HA results were observed with sheep cell tests, while horse cell tests showed more false-positives.
- Virtually all IM cases possessed EBV-VCA antibodies, contrasting with only half of the control group.
Conclusions:
- Horse cell microtitre and Monospot tests are more sensitive but yield more false-positives than sheep cell tests for IM diagnosis.
- Specific EBV-IgM and EBV-EA antibody tests are valuable for diagnosing selected borderline IM cases.
- The long-lasting nature of HA may lead to misinterpretation of false-positives in unrecognized past infections.