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Current Topics in Microbiology and... 2015Infectious mononucleosis is a clinical entity characterized by sore throat, cervical lymph node enlargement, fatigue, and fever most often seen in adolescents and young... (Review)
Review
Infectious mononucleosis is a clinical entity characterized by sore throat, cervical lymph node enlargement, fatigue, and fever most often seen in adolescents and young adults and lasting several weeks. It can be caused by a number of pathogens, but this chapter only discusses infectious mononucleosis due to primary Epstein-Barr virus (EBV) infection. EBV is a γ-herpesvirus that infects at least 90% of the population worldwide. The virus is spread by intimate oral contact among teenagers and young adults. How preadolescents acquire the virus is not known. A typical clinical picture with a positive heterophile test is usually sufficient to make the diagnosis, but heterophile antibodies are not specific and do not develop in some patients. EBV-specific antibody profiles are the best choice for staging EBV infection. In addition to causing acute illness, there can also be long-term consequences as the result of acquisition of the virus. Several EBV-related illnesses occur including certain cancers and autoimmune diseases, as well as complications of primary immunodeficiency in persons with the certain genetic mutations. A major obstacle to understanding these sequelae has been the lack of an efficient animal model for EBV infection, although progress in primate and mouse models has recently been made. Key future challenges are to develop protective vaccines and effective treatment regimens.
Topics: Animals; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Infectious Mononucleosis
PubMed: 26424648
DOI: 10.1007/978-3-319-22822-8_9 -
American Family Physician Mar 2015Epstein-Barr is a ubiquitous virus that infects 95% of the world population at some point in life. Although Epstein-Barr virus (EBV) infections are often asymptomatic,... (Review)
Review
Epstein-Barr is a ubiquitous virus that infects 95% of the world population at some point in life. Although Epstein-Barr virus (EBV) infections are often asymptomatic, some patients present with the clinical syndrome of infectious mononucleosis (IM). The syndrome most commonly occurs between 15 and 24 years of age. It should be suspected in patients presenting with sore throat, fever, tonsillar enlargement, fatigue, lymphadenopathy, pharyngeal inflammation, and palatal petechiae. A heterophile antibody test is the best initial test for diagnosis of EBV infection, with 71% to 90% accuracy for diagnosing IM. However, the test has a 25% false-negative rate in the first week of illness. IM is unlikely if the lymphocyte count is less than 4,000 mm3. The presence of EBV-specific immunoglobulin M antibodies confirms infection, but the test is more costly and results take longer than the heterophile antibody test. Symptomatic relief is the mainstay of treatment. Glucocorticoids and antivirals do not reduce the length or severity of illness. Splenic rupture is an uncommon complication of IM. Because physical activity within the first three weeks of illness may increase the risk of splenic rupture, athletic participation is not recommended during this time. Children are at the highest risk of airway obstruction, which is the most common cause of hospitalization from IM. Patients with immunosuppression are more likely to have fulminant EBV infection.
Topics: Adolescent; Airway Obstruction; Antibodies, Viral; Disease Management; Herpesvirus 4, Human; Humans; Immunoglobulin M; Infectious Mononucleosis; Serologic Tests; Splenic Rupture; Young Adult
PubMed: 25822555
DOI: No ID Found -
Annals of Laboratory Medicine Jan 2022Immunoassays are powerful qualitative and quantitative analytical techniques. Since the first description of an immunoassay method in 1959, advances have been made in... (Review)
Review
Immunoassays are powerful qualitative and quantitative analytical techniques. Since the first description of an immunoassay method in 1959, advances have been made in assay designs and analytical characteristics, opening the door for their widespread implementation in clinical laboratories. Clinical endocrinology is closely linked to laboratory medicine because hormone quantification is important for the diagnosis, treatment, and prognosis of endocrine disorders. Several interferences in immunoassays have been identified through the years; although some are no longer encountered in daily practice, cross-reaction, heterophile antibodies, biotin, and anti-analyte antibodies still cause problems. Newer interferences are also emerging with the development of new therapies. The interfering substance may be exogenous (e.g., a drug or substance absorbed by the patient) or endogenous (e.g., antibodies produced by the patient), and the bias caused by interference can be positive or negative. The consequences of interference can be deleterious when clinicians consider erroneous results to establish a diagnosis, leading to unnecessary explorations or inappropriate treatments. Clinical laboratories and manufacturers continue to investigate methods for the detection, elimination, and prevention of interferences. However, no system is completely devoid of such incidents. In this review, we focus on the analytical interferences encountered in daily practice and possible solutions for their detection or elimination.
Topics: Antibodies; Biotin; Cross Reactions; Hormones; Humans; Immunoassay
PubMed: 34374345
DOI: 10.3343/alm.2022.42.1.3 -
Clinical & Translational Immunology Feb 2015Infectious mononucleosis is a clinical entity characterized by pharyngitis, cervical lymph node enlargement, fatigue and fever, which results most often from a primary... (Review)
Review
Infectious mononucleosis is a clinical entity characterized by pharyngitis, cervical lymph node enlargement, fatigue and fever, which results most often from a primary Epstein-Barr virus (EBV) infection. EBV, a lymphocrytovirus and a member of the γ-herpesvirus family, infects at least 90% of the population worldwide, the majority of whom have no recognizable illness. The virus is spread by intimate oral contact among adolescents, but how preadolescents acquire the virus is not known. During the incubation period of approximately 6 weeks, viral replication first occurs in the oropharynx followed by viremia as early as 2 weeks before onset of illness. The acute illness is marked by high viral loads in both the oral cavity and blood accompanied by the production of immunoglobulin M antibodies against EBV viral capsid antigen and an extraordinary expansion of CD8(+) T lymphocytes directed against EBV-infected B cells. During convalescence, CD8(+) T cells return to normal levels and antibodies develop against EBV nuclear antigen-1. A typical clinical picture in an adolescent or young adult with a positive heterophile test is usually sufficient to make the diagnosis of infectious mononucleosis, but heterophile antibodies are not specific and do not develop in some patients especially young children. EBV-specific antibody profiles are the best choice for staging EBV infection. In addition to causing acute illness, long-term consequences are linked to infectious mononucleosis, especially Hodgkin lymphoma and multiple sclerosis. There is no licensed vaccine for prevention and no specific approved treatment. Future research goals are development of an EBV vaccine, understanding the risk factors for severity of the acute illness and likelihood of developing cancer or autoimmune diseases, and discovering anti-EBV drugs to treat infectious mononucleosis and other EBV-spurred diseases.
PubMed: 25774295
DOI: 10.1038/cti.2015.1 -
Frontiers in Immunology 2022Porcine islets surviving the acute injury caused by humoral rejection and IBMIR will be subjected to cellular xenograft rejection, which is predominately mediated by CD4... (Review)
Review
Porcine islets surviving the acute injury caused by humoral rejection and IBMIR will be subjected to cellular xenograft rejection, which is predominately mediated by CD4 T cells and is characterised by significant infiltration of macrophages, B cells and T cells (CD4 and CD8). Overall, the response is different compared to the alloimmune response and more difficult to suppress. Activation of CD4 T cells is both by direct and indirect antigen presentation. After activation they recruit macrophages and direct B cell responses. Although they are less important than CD4 T cells in islet xenograft rejection, macrophages are believed to be a major effector cell in this response. Rodent studies have shown that xenoantigen-primed and CD4 T cell-activated macrophages were capable of recognition and rejection of pancreatic islet xenografts, and they destroyed a graft the secretion of various proinflammatory mediators, including TNF-α, reactive oxygen and nitrogen species, and complement factors. B cells are an important mediator of islet xenograft rejection xenoantigen presentation, priming effector T cells and producing xenospecific antibodies. Depletion and/or inhibition of B cells combined with suppressing T cells has been suggested as a promising strategy for induction of xeno-donor-specific T- and B-cell tolerance in islet xenotransplantation. Thus, strategies that expand the influence of regulatory T cells and inhibit and/or reduce macrophage and B cell responses are required for use in combination with clinical applicable immunosuppressive agents to achieve effective suppression of the T cell-initiated xenograft response.
Topics: Animals; Antigens, Heterophile; Graft Rejection; Heterografts; Humans; Immunity, Cellular; Islets of Langerhans Transplantation; Swine; Transplantation, Heterologous
PubMed: 35874735
DOI: 10.3389/fimmu.2022.893985 -
Transplant Immunology Aug 2021Xenotransplantation, using genetically-modified pigs for clinical organ transplantation, is a solution to the organ shortage. The biggest barrier to clinical... (Review)
Review
Xenotransplantation, using genetically-modified pigs for clinical organ transplantation, is a solution to the organ shortage. The biggest barrier to clinical implementation is the antigenicity of pig cells. Humans possess preformed antibody to pig cells that initiate antibody-mediated rejection of pig organs in primates. Advances in genetic engineering have led to the development of a pig lacking the three known glycan xenoantigens (triple-knockout [TKO] pigs). A significant number of human sera demonstrate no antibody binding to TKO pig cells. As a result of the TKO pig's low antigen expression, survival of life-supporting pig organs in immunosuppressed nonhuman primates has significantly increased, and hope has been renewed for clinical trials of xenotransplantation. It is important to understand the context in which xenotransplantation's predecessor, allotransplantation, has been successful, and the steps needed for the success of xenotransplantation. Successful allotransplantation has been based on two main immunological approaches - (i) adequate immunosuppressive therapy, and (ii) careful histocompatibility matching. In vivo studies suggest that the available immunosuppressive regimens are adequate to suppress the human anti-pig cellular response. Methods to evaluate and screen patients for the first clinical xenotransplantation trial are the next challenge. The goal of this review is to summarize the history of histocompatibility testing, and the available tools that can be utilized to determine xenograft histocompatibility.
Topics: Animals; Animals, Genetically Modified; Antibodies, Heterophile; Antigens, Heterophile; Cells, Cultured; Gene Knockout Techniques; HLA Antigens; Histocompatibility; Histocompatibility Antigens Class I; Histocompatibility Testing; Humans; Polysaccharides; Swine; Tissue and Organ Procurement; Transplantation, Heterologous
PubMed: 34015463
DOI: 10.1016/j.trim.2021.101409