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JACC. Case Reports Aug 2020
PubMed: 34317027
DOI: 10.1016/j.jaccas.2020.07.008 -
JACC. Case Reports Aug 2020
PubMed: 34317026
DOI: 10.1016/j.jaccas.2020.05.108 -
Cureus Jun 2021Epstein-Barr virus (EBV) primary infection usually presents with classic symptoms of infectious mononucleosis (IM) like fever, lymphadenopathies and tonsillopharyngitis....
Epstein-Barr virus (EBV) primary infection usually presents with classic symptoms of infectious mononucleosis (IM) like fever, lymphadenopathies and tonsillopharyngitis. Liver damage is frequently mild and self-limited and there are only a few cases of severe EBV-induced cholestatic hepatitis and jaundice reported in the literature. The authors present the case of a 22-year-old woman who was admitted with acute fever and jaundice. Physical examination revealed posterior cervical lymphadenopathies and painful hepatosplenomegaly. Laboratorial findings suggested an obstructive cause for jaundice but ultrasound and magnetic resonance cholangiopancreatography excluded biliary duct pathology. Heterophile antibodies were negative but EBV-specific antibodies revealed isolated positive viral capsid antigen (VCA) immunoglobin (Ig) M suggesting the diagnosis of early phase of EBV primary infection. The diagnosis of EBV-induced cholestatic hepatitis was confirmed after identification of EBV deoxyribonucleic acid (DNA) in blood and by liver biopsy. Supportive management was provided and, despite an initial clinical deterioration, the patient had a favorable outcome. EBV is a virus with a high prevalence worldwide, mainly subclinical, and jaundice is a rare manifestation of the infection. Although the majority of the patients recover without sequelae, progression to liver failure has been described and a careful assessment for complications is mandatory. Therefore, EBV infection should be included in the comprehensive differential diagnosis of jaundice in all age groups.
PubMed: 34277228
DOI: 10.7759/cureus.15609 -
Science Translational Medicine Jul 2021The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune...
The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune responses. Experimental intranasal infection of human adults with the commensal produced safe, sustained pharyngeal colonization. This has potential utility as a vehicle for sustained release of antigen to the human mucosa, but commensals in general are thought to be immunologically tolerated. Here, we show that engineered , chromosomally transformed to express a heterologous vaccine antigen, safely induces systemic, antigen-specific immune responses during carriage in humans. When the expressing the meningococcal antigen Neisseria Adhesin A (NadA) was inoculated intranasally into human volunteers, all colonized participants carried the bacteria asymptomatically for at least 28 days, with most (86%) still carrying the bacteria at 90 days. Compared to an otherwise isogenic but phenotypically wild-type strain, colonization with NadA-expressing generated NadA-specific immunoglobulin G (IgG)- and IgA-secreting plasma cells within 14 days of colonization and NadA-specific IgG memory B cells within 28 days of colonization. NadA-specific IgG memory B cells were detected in peripheral blood of colonized participants for at least 90 days. Over the same period, there was seroconversion against NadA and generation of serum bactericidal antibody activity against a NadA-expressing meningococcus. The controlled infection was safe, and there was no transmission to adult bedroom sharers during the 90-day period. Genetically modified could therefore be used to generate beneficial immune responses to heterologous antigens during sustained pharyngeal carriage.
Topics: Adult; Antibodies, Bacterial; Antigens, Heterophile; Ecosystem; Humans; Immunologic Memory; Meningococcal Vaccines; Neisseria lactamica
PubMed: 34233953
DOI: 10.1126/scitranslmed.abe8573 -
International Journal of Laboratory... Feb 2022
Topics: Adult; Antibodies, Heterophile; COVID-19; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Hematologic Tests; Humans; Male; Middle Aged; SARS-CoV-2
PubMed: 34191392
DOI: 10.1111/ijlh.13654 -
Therapeutic Advances in Reproductive... 2021The scenario in which a patient tests positive for human chorionic gonadotropin (hCG) in the absence of pregnancy can pose a diagnostic dilemma for clinicians. The term... (Review)
Review
The scenario in which a patient tests positive for human chorionic gonadotropin (hCG) in the absence of pregnancy can pose a diagnostic dilemma for clinicians. The term "phantom hCG" refers to persistently positive hCG levels on diagnostic testing in a nonpregnant patient and such results often lead to a false diagnosis of malignancy and subsequent inappropriate treatment with chemotherapy or hysterectomy. There remains a need for a consistent and rational diagnostic approach to the "phantom hCG." This article aims to review the different etiologies of positive serum hCG testing in nonpregnant subjects and concludes with a practical, stepwise diagnostic approach to assist clinicians encountering this clinical dilemma.
PubMed: 34179786
DOI: 10.1177/26334941211016412 -
Scientific Reports Jun 2021Xenotransplantation (cross-species transplantation) using genetically-engineered pig organs offers a potential solution to address persistent organ shortage. Current...
Xenotransplantation (cross-species transplantation) using genetically-engineered pig organs offers a potential solution to address persistent organ shortage. Current evaluation of porcine genetic modifications is to monitor the nonhuman primate immune response and survival after pig organ xenotransplantation. This measure is an essential step before clinical xenotransplantation trials, but it is time-consuming, costly, and inefficient with many variables. We developed an efficient approach to quickly examine human-to-pig xeno-immune responses in vitro. A porcine endothelial cell was characterized and immortalized for genetic modification. Five genes including GGTA1, CMAH, β4galNT2, SLA-I α chain, and β2-microglobulin that are responsible for the production of major xenoantigens (αGal, Neu5Gc, Sda, and SLA-I) were sequentially disrupted in immortalized porcine endothelial cells using CRISPR/Cas9 technology. The elimination of αGal, Neu5Gc, Sda, and SLA-I dramatically reduced the antigenicity of the porcine cells, though the cells still retained their ability to provoke human natural killer cell activation. In summary, evaluation of human immune responses to genetically modified porcine cells in vitro provides an efficient method to identify ideal combinations of genetic modifications for improving pig-to-human compatibility, which should accelerate the application of xenotransplantation to humans.
Topics: Animals; Animals, Genetically Modified; Antibodies, Heterophile; Antigen-Antibody Reactions; Antigens, Heterophile; CRISPR-Cas Systems; Cell Degranulation; Cell Line, Transformed; Cytokines; Endothelial Cells; Galactosyltransferases; Gene Knockout Techniques; Graft Rejection; Histocompatibility Antigens Class I; Humans; Killer Cells, Natural; Liver; Lymphocyte Activation; Mixed Function Oxygenases; N-Acetylgalactosaminyltransferases; Swine; Transplantation, Heterologous; beta 2-Microglobulin
PubMed: 34162938
DOI: 10.1038/s41598-021-92543-y -
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 -
Acta Biochimica Et Biophysica Sinica May 2021The major etiologic agent that causes acute gastroenteritis worldwide in young animals and children is Group A rotavirus. Currently, commercially available vaccines do...
The major etiologic agent that causes acute gastroenteritis worldwide in young animals and children is Group A rotavirus. Currently, commercially available vaccines do not often prevent porcine rotavirus (PRV) infection. In this study, we evaluated the efficacy of oral recombinant Lactobacillus vaccine against PRV in a mouse model. Lactobacillus plantarum NC8 was used as the host strain, and bacterial vectors were constructed, because the NC8 isolated has shown the capability to survive gastric transit and to colonize the intestinal tract of humans and other mammals. To explore the immunological mechanisms, lactic acid bacterial vectors were used to express VP7 antigen from PRV. We constructed an L. plantarum strain with surface-displayed VP7, named NC8-pSIP409-pgsA-VP7-DCpep. The expressed recombinant protein had a molecular weight of ∼37 kDa. The strain was used to immunize BALB/c mice to evaluate their immunomodulatory characteristics. Mice were orally immunized with recombinant L. plantarum NC8-pSIP409-pgsA-VP7-DCpep at a dose of 2 × 109 colony forming units/200 µl. The results showed that NC8-pSIP409-pgsA-VP7-DCpep significantly stimulated the differentiation of dendritic cells (DCs) in Peyer's patches (PPs) and increased the serum levels of IL-4 and IFN-γ, as measured by enzyme-linked immunosorbent assay in mice treated with NC8-pSIP409-pgsA-VP7-DCpep. Compared to the empty vector group, NC8-pSIP409-pgsA-VP7-DCpep significantly increased the production of B220+ B cells in mesenteric lymph nodes (MLNs) and PPs and also increased the titer levels of the VP7-specific antibodies, including IgG and sIgA. The administration of NC8-pSIP409-pgsA-VP7-DCpep mediated relatively broad cellular responses. This study reveals that clear alternatives exist for PRV control strategies and provides information on PRV infection.
Topics: Animals; Antibodies, Viral; Antigens, Heterophile; Antigens, Viral; B-Lymphocytes; Capsid Proteins; Cytokines; Female; Genes, Viral; Genetic Engineering; Immunization; Immunogenicity, Vaccine; Immunoglobulin A, Secretory; Immunoglobulin G; Lactobacillus plantarum; Mice; Mice, Inbred BALB C; Recombinant Proteins; Rotavirus; Swine; Vaccines, Synthetic
PubMed: 33963824
DOI: 10.1093/abbs/gmab050 -
Xenotransplantation Jul 2021A major obstacle to the success of organ transplantation from pigs to humans, necessitated by the shortage of human organs, is robust humoral immune rejection by...
BACKGROUND
A major obstacle to the success of organ transplantation from pigs to humans, necessitated by the shortage of human organs, is robust humoral immune rejection by pig-reactive human antibodies. Mixed xenogeneic hematopoietic chimerism induces xenoreactive B cell tolerance in rodents, but whether mixed pig/human chimerism could induce tolerance of human B cells to pig xenoantigens is unknown.
METHODS
We investigated this question using a humanized mouse model in which durable mixed (pig-human) xenogeneic chimerism can be established.
RESULTS
Human natural anti-pig cytotoxic antibodies, predominantly IgM, are detectable in non-chimeric humanized mouse serum, and pig-reactive antibodies were reduced in mixed chimeric versus non-chimeric humanized mice. This difference required persistent mixed chimerism and was not due to the adsorption of antibodies on pig cells in vivo. Furthermore, human B cells from spleens of mixed chimeric mice produced lower levels of anti-pig antibodies when stimulated in vitro compared with those from non-chimeric mice.
CONCLUSIONS
Our findings demonstrate that mixed chimerism reduces human natural antibodies to pig xenoantigens, providing the first in vivo evidence of human B cell tolerance induction by mixed xenogeneic chimerism and supporting further evaluation of this approach for inducing human B cell tolerance to xenografts.
Topics: Animals; Antigens, Heterophile; B-Lymphocytes; Bone Marrow Transplantation; Chimerism; Humans; Immune Tolerance; Mice; Swine; Transplantation, Heterologous
PubMed: 33904221
DOI: 10.1111/xen.12691