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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 -
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 -
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 -
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 -
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 -
Frontiers in Veterinary Science 2022The genome contributes to the uniqueness of an individual breed, and enables distinctive characteristics to be passed from one generation to the next. The allelic... (Review)
Review
The genome contributes to the uniqueness of an individual breed, and enables distinctive characteristics to be passed from one generation to the next. The allelic heterogeneity of a certain breed results in a different response to a pathogen with different genomic expression. Disease resistance in chicken is a polygenic trait that involves different genes that confer resistance against pathogens. Such resistance also involves major histocompatibility (MHC) molecules, immunoglobulins, cytokines, interleukins, T and B cells, and CD4+ and CD8+ T lymphocytes, which are involved in host protection. The MHC is associated with antigen presentation, antibody production, and cytokine stimulation, which highlight its role in disease resistance. The natural resistance-associated macrophage protein 1 (Nramp-1), interferon (IFN), myxovirus-resistance gene, myeloid differentiation primary response 88 (MyD88), receptor-interacting serine/threonine kinase 2 (RIP2), and heterophile cells are involved in disease resistance and susceptibility of chicken. Studies related to disease resistance genetics, epigenetics, and quantitative trait loci would enable the identification of resistance markers and the development of disease resistance breeds. Microbial infections are responsible for significant outbreaks and have blighted the poultry industry. Breeding disease-resistant chicken strains may be helpful in tackling pathogens and increasing the current understanding on host genetics in the fight against communicable diseases. Advanced technologies, such as the CRISPR/Cas9 system, whole genome sequencing, RNA sequencing, and high-density single nucleotide polymorphism (SNP) genotyping, aid the development of resistant breeds, which would significantly decrease the use of antibiotics and vaccination in poultry. In this review, we aimed to reveal the recent genetic basis of infection and genomic modification that increase resistance against different pathogens in chickens.
PubMed: 36439341
DOI: 10.3389/fvets.2022.1032983