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American Family Physician Jan 2023Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and... (Review)
Review
Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. The heterophile antibody test has a sensitivity of 87% and specificity of 91% but can have a false-negative result in children younger than five years and in adults during the first week of illness. The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. Epstein-Barr viral capsid antigen-antibody testing is more sensitive and specific but more expensive and takes longer to process than the rapid heterophile antibody test. Treatment of infectious mononucleosis is supportive; routine use of antivirals and corticosteroids is not recommended. Current guidelines recommend that patients with infectious mononucleosis not participate in athletic activity for three weeks from onset of symptoms. Shared decision-making should be used to determine the timing of return to activity. Immunosuppressed populations are at higher risk of severe disease and significant morbidity. Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases.
Topics: Adolescent; Child; Humans; Antibodies, Heterophile; Antibodies, Viral; Autoimmune Diseases; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Infectious Mononucleosis
PubMed: 36689975
DOI: No ID Found -
Endocrine Journal Dec 2020The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the...
The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the safety profiles of this strategy remain uncharacterized. We evaluated three patients who exhibited elevated serum parathyroid hormone (PTH) levels without the relevant clinical manifestations and had a history of autologous NK cell therapy. The serum PTH concentration was measured using a second-generation PTH assay, and the serum thyroglobulin concentration was measured using a second-generation thyroglobulin assay. Subsequently, the PTH or thyroglobulin concentration obtained using heterophile-blocking tube (HBT) for a secondary confirmation assay was measured and compared with the result of the initial assay. The three patients had falsely elevated serum PTH and thyroglobulin levels owing to heterophile antibody interference associated with NK cell therapy that persisted for at least up to 12 months after the treatment and was confirmed by normalization of hormone levels after HBT treatment. We propose that certain types of mouse monoclonal antibodies used to stimulate NK cells can induce heterophile antibodies. Abnormal laboratory test results in individuals administered NK cell therapy without the relevant clinical manifestations must be examined in the context of heterophile antibody interference to avoid misdiagnosis and unnecessary testing.
Topics: Adoptive Transfer; Aged; Antibodies, Heterophile; Female; Humans; Immunotherapy; Killer Cells, Natural; Male; Middle Aged; Neoplasm Recurrence, Local; Parathyroid Hormone; Thyroglobulin; Thyroid Neoplasms
PubMed: 32713865
DOI: 10.1507/endocrj.EJ20-0349 -
Clinica Chimica Acta; International... Oct 2019Analysis of many clinically important analytes is dependent on antibody-based assays. However, depending on the design, these assays are vulnerable to interference from...
BACKGROUND
Analysis of many clinically important analytes is dependent on antibody-based assays. However, depending on the design, these assays are vulnerable to interference from endogenous molecules including circulating antibodies and free biotin. In this case report, we describe a patient whose laboratory findings from immunoassay based methodologies, are inconsistent with the clinical presentation.
CASE PRESENTATION
A 14-year-old male was referred to Pediatric Endocrinology for suspected hyperthyroidism based on critically elevated free thyroxine (fT4) levels although clinical assessment was inconsistent with hyperthyroidism. Because repeat testing was discrepant, Endocrinology questioned the validity of the results prompting consultation with the laboratory to investigate the source of the inconsistent findings. Review of discordant results revealed that fT4 levels measured in laboratories utilizing Roche instrumentation were critically high, while results from laboratories using alternative platforms (i.e. Siemens Centaur) were within normal limits.
CONCLUSION
After a comprehensive evaluation which included testing of paired specimens on multiple platforms, measurement of serially diluted specimens and a formal evaluation for the presence of heterophile antibodies, it was determined that a heterophile antibody interference was the most likely cause of the aberrant results in this patient.
Topics: Adolescent; Antibodies, Heterophile; Humans; Immunoassay; Male
PubMed: 31325446
DOI: 10.1016/j.cca.2019.07.010 -
Archives of Disease in Childhood.... Aug 2017Epstein-Barr virus (EBV) is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious...
Epstein-Barr 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 occurring during EBV infection. Heterophile antibody tests are rapid, cheap and specific tests that can be performed from the onset of symptoms of infectious mononucleosis. In adolescents, heterophile antibody tests have high specificity and sensitivity in the diagnosis of primary acute EBV infection. However, the tests have low sensitivity and low negative predictive value in young children and are not useful under the age of 4. Heterophile tests may be positive in other viral infections, autoimmune disease and haematological malignancies, but do not appear to be positive in primary bacterial infection. Virus-specific serology is required in children under the age of 4 or if an older child is heterophile negative. Virus-specific serology allows diagnosis and the pattern of positivity and negativity enables the clinician to stage the EBV infection. Virus-specific serology appears to have better sensitivity in young children, but there is cross-reaction with other herpesvirus infections, a longer turnaround time and it is more expensive to perform. Further research is needed to establish which children benefit from and hence require testing for heterophile antibodies, the cost-effectiveness of EBV investigations and whether heterophile titres have predictive value for the severity of infection and the likelihood of complications.
Topics: Adolescent; Antibodies, Heterophile; Antibodies, Viral; Child; Child, Preschool; Diagnostic Techniques and Procedures; Epstein-Barr Virus Infections; Female; Humans; Infectious Mononucleosis; Male
PubMed: 28130396
DOI: 10.1136/archdischild-2016-311526 -
Clinica Chimica Acta; International... Nov 2002Heterophile antibodies interfere with immunoassays. Understanding the nature and characteristics of these antibodies provides a format for better identifying and... (Review)
Review
BACKGROUND
Heterophile antibodies interfere with immunoassays. Understanding the nature and characteristics of these antibodies provides a format for better identifying and removing them. Growing evidence suggests many of these antibodies are natural antibodies. Very large number of tests are being performed with automated analyzers and there has been a problem with misdiagnosis due to interference. New commercial agents for blocking heterophile antibodies have been developed.
METHODS
Review of the immunology and methodological literature with critical interpretation of the findings.
CONCLUSIONS
Heterophile antibodies consist of natural antibodies and autoantibodies. Both types are usually weak antibodies that interfere by noncompetitive mechanisms. Based on very strong circumstantial evidence, we propose that natural antibodies account for most interference with automated immunoassays. In terms of false positive results, the interference rate is very low, about 99.95% accuracy. Specific blocking agents have some theoretical advantage over nonspecific blocking agents, but in actual practice, the very low false positive frequency makes it difficult if not impossible to statistically compare blocking agents or other assay modifications with adequate statistical power. In the absence of a technique that lends itself to automation for removing all immunoglobulins, it appears that infrequent heterophile interference cannot be avoided.
Topics: Animals; Antibodies, Heterophile; Antibody Specificity; Diagnostic Errors; Humans; Immunoassay
PubMed: 12367762
DOI: 10.1016/s0009-8981(02)00275-9 -
Journal of Medical Virology Nov 2021Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein-Barr virus. Seven commercially available assays... (Comparative Study)
Comparative Study
Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein-Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation.
Topics: Adolescent; Antibodies, Heterophile; Antibodies, Viral; Child; Clinical Laboratory Techniques; Epstein-Barr Virus Infections; Humans; Immunoglobulin M; Infectious Mononucleosis; Reagent Kits, Diagnostic; Young Adult
PubMed: 34347299
DOI: 10.1002/jmv.27254 -
Indian Journal of Pediatrics Jan 2004The present study has been carried out to analyse the trend of heterophile antibody positive infectious mononucleosis cases. (Comparative Study)
Comparative Study
OBJECTIVE
The present study has been carried out to analyse the trend of heterophile antibody positive infectious mononucleosis cases.
METHODS
A total of 1741 cases of clinically suspected infectious mononucleosis from various age groups were investigated during the period January, 1986 to December, 2000 and were analysed for infectious mononucleosis (IM) specific heterophile antibody by Paul-Bunnel-Davidsohn (PBD) test. Forty seven heterophile antibody negative samples were also tested simultaneously for the presence of the IgG antibody to viral capsid antigen (VCA) and Epstein Barr nuclear antigen (EBNA) to detect the exposure to Epstein Barr Virus (EBV) infection.
RESULTS
The overall percentage of EBV specific heterophile (Paul-Bunnel) antibody positivity was found to be 11.1% (194/1741). The average Paul-Bunnel antibody positivity between 1986 to 1990 was 20.5% which declined drastically to 5.7% during 1991-2000. Males comprised of 55.2% of the serologically proven IM cases. Of the 47 heterophile antibody negative cases, 38 (80.9%) and 33 (70.2%) were found to be positive for anti-VCA IgG and anti-EBNA IgG antibodies respectively. Paul Bunnel antibody positivity was found to be higher in >14 year age group patients than those below 14 years.
CONCLUSION
These findings suggest that the EBV infection still continues to be endemic in this part of the country, however, a declining trend in IM cases was observed during the last decade.
Topics: Adolescent; Age Distribution; Antibodies, Heterophile; Antibodies, Viral; Chi-Square Distribution; Child; Child, Preschool; Cohort Studies; Developing Countries; Endemic Diseases; Female; Herpesvirus 4, Human; Humans; Incidence; India; Infectious Mononucleosis; Male; Probability; Retrospective Studies; Risk Assessment; Serologic Tests; Sex Distribution
PubMed: 14979379
DOI: 10.1007/BF02725649 -
Best Practice & Research. Clinical... Oct 2013Immunometric assays are inherently vulnerable to interference from heterophilic antibodies, endogenous antibodies that bind assay antibodies. The consequences of such... (Review)
Review
Immunometric assays are inherently vulnerable to interference from heterophilic antibodies, endogenous antibodies that bind assay antibodies. The consequences of such interference can be devastating. In this review, we discuss strategies that reduce the damage caused by heterophilic antibodies. Clinicians should only order blood tests that are indicated for the patient and clinical setting at hand, and have the confidence to question laboratory results discordant with the clinical picture. Laboratorians should familiarize themselves with the vulnerability of the assays they offer, and be able to perform and interpret adequate confirmatory measures correctly. When designing immunoassays, the immunoassay industry should invest the necessary resources in specific protective measures against heterophilic antibody interference. Examples include using antibody fragments and the addition of effective blockers to assay reagents. The increasing use of modified monoclonal mouse antibodies both in therapy and diagnostics could present a particular challenge in the future.
Topics: Animals; Antibodies, Heterophile; Antibodies, Monoclonal; Humans; Immunoassay; Immunoglobulin Fc Fragments; Mice; Rheumatoid Factor; Sensitivity and Specificity
PubMed: 24094636
DOI: 10.1016/j.beem.2013.05.011 -
Clinical Biochemistry Jun 2016This case report investigates the origin of a false positive result on a serum qualitative human chorionic gonadotropin (hCG) device.
OBJECTIVES
This case report investigates the origin of a false positive result on a serum qualitative human chorionic gonadotropin (hCG) device.
PATIENT AND METHODS
A 46-year-old woman diagnosed with chronic myeloid leukemia presented with nausea and vomiting. A qualitative serum hCG test was interpreted as positive; however, a quantitative serum hCG test was negative (<5IU/L). To further investigate this discrepancy, the sample was pretreated with heterophilic blocking reagent (HBR). Additionally, the sample was tested on other qualitative hCG devices composed of antibodies from different animal sources. Blocking reagent from an automated quantitative immunoassay was also tested for its ability to inhibit the heterophile antibody interference.
RESULTS
The qualitative test result was negative after pretreatment with heterophilic blocking reagent. Other devices composed of antibodies from different animal sources also demonstrated mixed results with the patient's sample. Blocking reagent obtained from the automated quantitative assay inhibited the heterophile antibody interference in the patient's sample.
CONCLUSION
This case demonstrates that positive serum point-of-care hCG results should be interpreted with caution and confirmed with a quantitative serum hCG immunoassay when clinical suspicion is raised.
Topics: Antibodies, Heterophile; Biomarkers; Chorionic Gonadotropin; False Positive Reactions; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Molecular Diagnostic Techniques; Point-of-Care Systems; Prognosis; Urinalysis
PubMed: 26968106
DOI: 10.1016/j.clinbiochem.2015.12.018 -
Clinical Biochemistry Apr 1992Recent findings indicate that many endogenous antibodies exhibit multispecificity. These antibodies exhibit a potential for interference with immunoassays. Antibodies... (Review)
Review
Recent findings indicate that many endogenous antibodies exhibit multispecificity. These antibodies exhibit a potential for interference with immunoassays. Antibodies that interfere with immunoassays have been called heterophile or heterophilic antibodies. The purpose of this review is: (1) to identify the nature of heterophile antibodies; (2) to delineate the processes that produce them; (3) to examine the mechanisms by which these antibodies cause interference; and (4) to explore how this information can be used to reduce immunoassay interference. In addition to producing specific antibodies, the process of antibody production gives rise to rudimentary antibodies that are polyspecific; e.g., the antigen-combining site has an affinity for antigens of different chemical composition. This process also generates idiotypic antibodies containing cross-reactive idiotopes. These antibodies along with rheumatoid factors, which are themselves polyspecific and rich in cross-reactive idiotopes, are inherent parts of the process of antibody production, and exhibit multispecificity. Mechanisms by which these antibodies cause immunoassay interference are outlined. These properties of antibodies may have substantial consequence in directing future assays toward greater clinical predictive value.
Topics: Animals; Antibodies, Heterophile; Antibody Specificity; Cross Reactions; Humans; Immunoassay
PubMed: 1623581
DOI: 10.1016/0009-9120(92)80048-l