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Current Pediatric Reviews 2024Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and... (Review)
Review
BACKGROUND
Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised.
OBJECTIVE
The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis.
METHODS
A search was conducted in October 2022 in PubMed Clinical Queries using the key terms "infectious mononucleosis" OR "Epstein-Barr virus" OR "EBV". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the aforementioned search was used in the compilation of the present article.
RESULTS
Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adolescents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fatigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count. The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery.
CONCLUSION
Infectious mononucleosis is generally a benign and self-limited disease. Prompt diagnosis is essential to avoid unnecessary investigations and treatments and to minimize complications. Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible, the most effective way to prevent EBV infection and infectious mononucleosis is the development of an effective, safe, and affordable EBV vaccine that can confer life-long immunity.
Topics: Adolescent; Young Adult; Humans; Infectious Mononucleosis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Splenomegaly; Antibodies, Heterophile; Splenic Rupture
PubMed: 37526456
DOI: 10.2174/1573396320666230801091558 -
Journal of the American Heart... Jun 2024Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic... (Review)
Review
Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.
Topics: Humans; Biomarkers; Autoantibodies; Heart Diseases; Predictive Value of Tests; Troponin I; Prognosis
PubMed: 38879450
DOI: 10.1161/JAHA.123.035128 -
Clinical Chemistry and Laboratory... Jul 2023The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the...
The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.
Topics: Humans; Myocardial Infarction; Biomarkers; Chemistry, Clinical; Antibodies; Troponin
PubMed: 36952681
DOI: 10.1515/cclm-2023-0028 -
Clinical Biochemistry Nov 2023Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of...
BACKGROUND
Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of interference are lacking. This study evaluated the effects of tmabs used in cancers ipilimumab (Bristol Myers Squibb), nivolumab (Bristol Myers Squibb), pembrolizumab (Merck) and autoimmune disorders adalimumab (AbbVie), infliximab (Janssen) and vedolizumab (Takeda) in common immunoassays used in the clinical laboratory.
METHODS
Residual sera from 10 randomly chosen patients were split into two tubes and spiked with same volume (approximately 5 % final volume) of either saline (control) or 6 tmabs (final concentration of 100 μg/mL each). Concentrations from sixteen analytes in 19 different assays were assessed: TSH (Roche and Beckman), free thyroxine (Roche and Siemens), cortisol (Beckman), Cancer Antigens (CA): CA19-9 (Beckman), CA15-3 (Roche), CA125 (Roche), and CA27.29 (Siemens), carcinoembryonic antigen (Beckman), alpha-fetoprotein (Beckman), thyroglobulin (Beckman) and thyroglobulin antibodies (Beckman), thyroid peroxidase antibody (Beckman), beta-human chorionic gonadotropin (Roche and Beckman), total prostate-specific antigen (Roche), parathyroid hormone (Roche) and antinuclear antibodies IgG (Werfen). The tmab spiked residual sera were compared with matched saline spiked sera and percent error was assessed against allowable total error defined from biological variation or CLIA limits.
RESULTS
None of the tested immunoassays were affected by the presence of the tmabs, in samples within or outside assay reference intervals. The median % error among all immunoassays ranged between -2.0% (for TSH) to 2.7% (for TPO Ab assay).
CONCLUSION
These findings demonstrate no detectable tmab interference for the assessed immunoassays using spiked preparations of the tmabs in residual human sera. The findings are limited to the tmabs and immunoassays studied here.
Topics: Male; Humans; Antibodies, Monoclonal; Thyroglobulin; Immunoassay; Autoimmune Diseases; Thyrotropin
PubMed: 37972806
DOI: 10.1016/j.clinbiochem.2023.110685 -
Frontiers in Immunology 2023Microbial infections are associated with the occurrence of autoimmune diseases, but the mechanisms of microbial infection inducing autoimmune diseases are not fully...
INTRODUCTION
Microbial infections are associated with the occurrence of autoimmune diseases, but the mechanisms of microbial infection inducing autoimmune diseases are not fully understood. The existence of heterophilic antigens between microorganisms and human tissues may explain part of the pathogenesis of autoimmune diseases. Here, we investigate the distribution of heterophilic antigens and its relationship with autoimmune diseases.
METHODS
Monoclonal antibodies against a variety of microorganisms were prepared. The titer, subclass and reactivity of antibodies with microorganisms were identified, and heterophilic antibodies that cross-reacted with human tissues were screened by human tissue microarray. The reactivity of these heterophilic antibodies with different individuals and different species was further examined by immunohistochemistry.
RESULTS
In this study, 21 strains of heterophilic antibodies were screened. The results showed that these heterophilic antibodies were produced due to the existence of heterophilic antigens between microorganism and human body and the distribution of heterophilic antigens had individual, tissue and species differences.
CONCLUSION
Our study showed that heterophilic antigens exist widely between microorganisms and human body, and the heterophilic antigens carried by microorganisms may break the immune tolerance of the body through carrier effect and initiate immune response, which may be one of the important mechanisms of infection inducing autoimmune diseases.
Topics: Humans; Antigens, Heterophile; Autoimmune Diseases; Antibodies, Monoclonal; Antibodies, Heterophile; Immunohistochemistry
PubMed: 38022676
DOI: 10.3389/fimmu.2023.1275658 -
Xenotransplantation 2024Xenoantigens other than Gal, Neu5Gc, and Sda may be playing a role in pig graft rejection. We investigated the incidence of antibodies to unknown pig xenoantigen in...
BACKGROUND
Xenoantigens other than Gal, Neu5Gc, and Sda may be playing a role in pig graft rejection. We investigated the incidence of antibodies to unknown pig xenoantigen in different human groups.
METHODS
We collected blood from TKO/hCD55 pigs (n = 3), and isolated PBMCs and RBCs. Serum samples were collected from (i) healthy human volunteers (n = 43), (ii) patients with end-stage renal disease (ESRD) (n = 87), (iii) the same patients after kidney allotransplantation (n = 50), and (iv) renal allotransplant recipients experiencing T cell-mediated rejection (allo-TCMR, n = 10). The sera were initially incubated with TKO/hCD55 pRBCs (1 × 10 cells) for 1 h to absorb anti-pig antibodies (except against SLA and possibly other antigens not expressed on pRBCs) and then the serum (absorbed or unabsorbed) was tested for antibody binding and complement-dependent cytotoxicity (CDC) to TKO/hCD55 pig PBMCs.
RESULTS
A significant reduction in IgM/IgG binding and CDC was observed in the absorbed sera. Serum obtained before and after renal allotransplantation showed no significant difference in IgM or IgG binding to, or in CDC of, TKO/hCD55 pig cells. IgM antibodies (but rarely IgG) against unknown xenoantigens expressed on TKO/hCD55 PBMCs, possibly against swine leukocyte antigens, were documented in healthy humans, patients with ESRD, and those with renal allografts undergoing acute T cell rejection. IgM (but not CDC) was higher in patients experiencing allo-TCMR.
CONCLUSION
Human sera contain IgM antibodies against unknown pig xenoantigens expressed on TKO/hCD55 pPBMCs. Although not confirmed in the present study, the targets for these antibodies may include swine leukocyte antigens.
Topics: Animals; Humans; Swine; Animals, Genetically Modified; Antigens, Heterophile; Incidence; Transplantation, Heterologous; Immunoglobulin M; Immunoglobulin G; Kidney Failure, Chronic; HLA Antigens; Graft Rejection
PubMed: 37529830
DOI: 10.1111/xen.12818 -
The Journal of Clinical Endocrinology... Mar 2024Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative...
Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine and/or free triiodothyronine measurements with nonsuppressed TSH levels. Different types of analytical interference (eg, abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (eg, resistance to thyroid hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumor) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artifact, followed by genetic testing or specialized imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy.
Topics: Humans; Thyroxine; Triiodothyronine; Thyroid Hormones; Thyrotropin; Thyroid Function Tests
PubMed: 37988295
DOI: 10.1210/clinem/dgad681