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The Journal of Experimental Medicine May 1953The cells of a human epithelial cancer cultivated en masse have been shown to support the multiplication of all three types of poliomyelitis virus. These cells (strain...
Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix.
The cells of a human epithelial cancer cultivated en masse have been shown to support the multiplication of all three types of poliomyelitis virus. These cells (strain HeLa of Gey) have been maintained in vitro since their derivation from an epidermoid carcinoma of the cervix in February, 1951. As the virus multiplied it caused in from 12 to 96 hours degeneration and destruction of the cancer cells. The specific destructive effect of the virus was prevented by adding homotypic antibody to the cultures but not by adding heterotypic antibodies. Methods for the preparation of large numbers of replicate cultures with suspensions of strain HeLa cells were described. The cells in suspension were readily quantitated by direct counts in a hemocytometer. A synthetic solution that maintains cellular viability was employed for viral propagation. The experimental results demonstrate the usefulness of strain HeLa cells for (a) the quantitation of poliomyelitis virus, (b) the measurement of poliomyelitis antibodies, and (c) the production of virus.
Topics: Antibodies; Antibodies, Heterophile; Carcinoma, Squamous Cell; Cervix Uteri; Female; HeLa Cells; Humans; In Vitro Techniques; Poliomyelitis; Poliovirus; Tissue Culture Techniques; Viruses
PubMed: 13052828
DOI: 10.1084/jem.97.5.695 -
Frontiers in Immunology 2020Seventy to ninety percentage of preformed xenoreactive antibodies in human serum bind to the galactose-α(1,3)-galactose Gal epitope, and the creation of Gal knockout... (Review)
Review
Seventy to ninety percentage of preformed xenoreactive antibodies in human serum bind to the galactose-α(1,3)-galactose Gal epitope, and the creation of Gal knockout (KO) pigs has eliminated hyperacute rejection as a barrier to xenotransplantation. Now other glycan antigens are barriers to move ahead with xenotransplantation, and the N-glycolyl neuraminic acid, Neu5Gc (or Hanganutziu-Deicher antigen), is also a major pig xenoantigen. Humans have anti-Neu5Gc antibodies. Several data indicate a strong immunogenicity of Neu5Gc in humans that may contribute to an important part in antibody-dependent injury to pig xenografts. Pig islets express Neu5Gc, which reacted with diet-derived human antibodies and mice deleted for Neu5Gc reject pancreatic islets from wild-type counterpart. However, Neu5Gc positive heart were not rejected in Neu5Gc KO mice indicating that the role of Neu5Gc-specific antibodies has to be nuanced and depend of the graft situation parameters (organ/tissue, recipient, implication of other glycan antigens). Recently generated Gal/Neu5Gc KO pigs eliminate the expression of Gal and Neu5Gc, and improve the crossmatch of humans with the pig. This review summarizes the current and recent experimental and (pre)clinical data on the Neu5Gc immunogenicity and emphasize of the potential impact of anti-Neu5Gc antibodies in limiting xenotransplantation in humans.
Topics: Animals; Antibodies, Heterophile; Disease Models, Animal; Gene Knockout Techniques; Graft Rejection; Heterografts; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Neuraminic Acids; Swine; Transplantation, Heterologous
PubMed: 32351506
DOI: 10.3389/fimmu.2020.00622 -
Xenotransplantation Jul 2019The role of complement in xenotransplantation is well-known and is a topic that has been reviewed previously. However, our understanding of the immense complexity of its... (Review)
Review
The role of complement in xenotransplantation is well-known and is a topic that has been reviewed previously. However, our understanding of the immense complexity of its interaction with other constituents of the innate immune response and of the coagulation, adaptive immune, and inflammatory responses to a xenograft is steadily increasing. In addition, the complement system plays a function in metabolism and homeostasis. New reviews at intervals are therefore clearly warranted. The pathways of complement activation, the function of the complement system, and the interaction between complement and coagulation, inflammation, and the adaptive immune system in relation to xenotransplantation are reviewed. Through several different mechanisms, complement activation is a major factor in contributing to xenograft failure. In the organ-source pig, the detrimental influence of the complement system is seen during organ harvest and preservation, for example, in ischemia-reperfusion injury. In the recipient, the effect of complement can be seen through its interaction with the immune, coagulation, and inflammatory responses. Genetic-engineering and other therapeutic methods by which the xenograft can be protected from the effects of complement activation are discussed. The review provides an updated source of reference to this increasingly complex subject.
Topics: Adaptive Immunity; Animals; Animals, Genetically Modified; Antibodies, Heterophile; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Complement Activation; Complement System Proteins; Endothelium, Vascular; Graft Rejection; Heterografts; Humans; Immunosuppressive Agents; Inflammasomes; Inflammation; Primates; Receptors, Complement; Swine; Tissue and Organ Harvesting; Transplantation Immunology; Transplantation, Heterologous
PubMed: 31033064
DOI: 10.1111/xen.12517 -
TouchREVIEWS in Endocrinology Nov 2022For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and... (Review)
Review
For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and other analytical components. Despite the differences between commercial products, these assays provide important clinical information about hormone levels in patients. However, inaccurate results can occur because of technical issues, as well as patient-specific factors that can interfere with immunoassay hormone measurements. The latter include excessive normal blood or serum components, the presence of cross-reacting substances, extremely high levels of hormones leading to the high-dose hook effect, and interference from a variety of endogenous factors such as human antibodies that interact with the assay components or high levels of biotin in the serum from exogenous ingestion. This article briefly reviews the sources and recognition of endogenous interference, and describes methods to determine the correct serum hormone concentration.
PubMed: 36694886
DOI: 10.17925/EE.2022.18.2.141 -
Endocrine Jun 2021Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to...
Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions leading to misdiagnosis. The most popular pitfalls are: acute physical and psychological stress, macroprolactin, hook effect, even though antibodies interferences and biotine use have to be considered. A 52-year-old woman was referred to Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval: <24 ng/ml) measured with the ECLIA immunoassay analyzer Elecsys 170. The patient's pituitary MRI was normal and macroprolactin was normal. Hormonal workup showed LH: 71.5 mU/ml (2-10.9 mU/ml), FSH: 111.4 mU/ml (3.9-8.8 mU/ml), Estradiol: 110.7 pg/mL (27-122 pg/ml). Since an interference was suspected, the sample was sent to another laboratory using a different assay. After antibody blocking tubes treatment (Heterophilic Blocking Tube, Scantibodies) PRL was 28.8 ng/ml (reference interval < 29.2 ng/ml). Analytical interference should be suspected when assay results are not consistent with the clinical picture. Endogenous antibodies (EA) include heterophile, human anti-animal, autoimmune and other nonspecific antibodies, and rheumatoid factors, that have structural similarities and can cross-react with the antibodies employed by the immunoassay, causing hyperprolactinemia misdiagnosis. The patient's job (butcher), led us to suspect the presence of anti-animal antibodies. Clinicians should also carefully investigate the use of supplements. Biotin can falsely increase hormone concentration in competitive assays. Many clinicians are still not informed about these pitfalls that are not mentioned in some recent reviews on PRL measurement.
Topics: Antibodies; Diagnostic Errors; Female; Humans; Hyperprolactinemia; Immunoassay; Middle Aged; Prolactin
PubMed: 32949349
DOI: 10.1007/s12020-020-02497-w -
The Clinical Biochemist. Reviews Aug 2008* Interference occurs when a substance or process falsely alters an assay result. * Interferences are classified as endogenous or exogenous. Endogenous interference...
* Interference occurs when a substance or process falsely alters an assay result. * Interferences are classified as endogenous or exogenous. Endogenous interference originates from substances present in the patient's own specimen. Exogenous interferences are substances introduced into the patient's specimen. * To perform interference studies, proper planning is required. * Interference from haemolysis, icterus and lipaemia are most frequently studied. Haemolysis affects more analytes than does any other type of interference. * Protein interferences are most often associated with paraproteins and predominantly with IgM or IgG and rarely with IgA. * Drug interference may be due to the parent drug, metabolite(s) or additives in the drug preparation. * Collection tube components can affect determination of analytes. * Carryover interference typically occurs when analyte from a high concentration sample (or reagent) is incompletely removed by the analytical system's washing process, whether probe, mixer or cuvette washing. * Immunoassay interferences are most commonly due to antibodies (generally polyclonal). They may be autoantibodies (e.g. in thyroid disease) or heterophile antibodies that predominantly interfere in two-site immunometric (sandwich) assays, forming a bridge between capture and detection antibodies. * Determining if interference is significant requires deviation limits from the original result. * Once interferences are identified during method evaluation or in general use, there is a need to establish procedures for handling affected results as part of the quality system.
PubMed: 18852856
DOI: No ID Found -
Journal of Clinical Laboratory Analysis Feb 2019Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level...
BACKGROUND
Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article.
METHODS
Serum from two patients with significantly elevated levels of D-dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D-dimer false positives and made a systematic review of the literature.
RESULTS
The D-dimer values were normal (0.49 and 0.15 μg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody.
CONCLUSIONS
The influence of heterophilic antibodies on the measurement of D-dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D-dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.
Topics: Aged; Aged, 80 and over; Antibodies, Heterophile; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunoassay; Reproducibility of Results
PubMed: 30320416
DOI: 10.1002/jcla.22687 -
Journal of Medical Virology Jul 2021Coronavirus disease 2019 (COVID-19) has brought a huge impact on global health and the economy. Early diagnosis of severe acute respiratory syndrome coronavirus 2... (Review)
Review
Coronavirus disease 2019 (COVID-19) has brought a huge impact on global health and the economy. Early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential for epidemic prevention and control. The detection of SARS-CoV-2 antibodies is an important criterion for diagnosing COVID-19. However, SARS-CoV-2 antibody testing also has certain false positives causing confusion in clinical diagnosis. This article summarizes the causes of false-positive detection of SARS-CoV-2 antibodies in clinical practice. The results indicate that the most common endogenous interferences include rheumatoid factor, heterophile antibodies, human anti-animal antibodies, lysozyme, complement, and cross-antigens. The exogenous interference is mainly incomplete coagulation of the specimen, contamination of the specimen, and insufficient optimization of the diagnostic kit's reaction system.
Topics: Antibodies, Viral; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; False Positive Reactions; Humans; Immunologic Tests; SARS-CoV-2
PubMed: 33710634
DOI: 10.1002/jmv.26937 -
The Yale Journal of Biology and Medicine 1982Epsten-Barr virus oropharyngeal shedding has been demonstrated in infectious mononucleosis patients many months after acute illness and long after the disease hallmarks,... (Review)
Review
Epsten-Barr virus oropharyngeal shedding has been demonstrated in infectious mononucleosis patients many months after acute illness and long after the disease hallmarks, atypical lymphocytes and heterophile antibody, have disappeared. Extracellular virus is present more frequently in saliva than in other oropharyngeal samples. Prolonged excretion of EBV in asymptomatic carriers explains the difficulty in tracing case-to-case spread and increased transmissibility in age groups in which salivary exchange is high.
Topics: Adolescent; Adult; Antibodies, Viral; Child; Child, Preschool; Female; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Infectious Mononucleosis; Male; Oropharynx; Saliva; Salivary Glands; Time Factors
PubMed: 6295004
DOI: No ID Found -
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