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Primary Immunodeficiency

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https://www.readbyqxmd.com/read/29145505/spontaneous-development-of-epstein-barr-virus-associated-human-lymphomas-in-a-prostate-cancer-xenograft-program
#1
Alberto J Taurozzi, Ramprakash Beekharry, Michelle Wantoch, Marie-Christine Labarthe, Hannah F Walker, Robert I Seed, Matthew Simms, Greta Rodrigues, James Bradford, Geertje van der Horst, Gabri van der Pluijm, Anne T Collins
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/29143337/intraductal-papillary-mucinous-neoplasm-of-the-pancreas-rapidly-xenografts-in-chicken-eggs-and-predicts-aggressiveness
#2
Zhefu Zhao, Nathalie Bauer, Ewa Aleksandrowicz, Libo Yin, Jury Gladkich, Wolfgang Gross, Jörg Kaiser, Thilo Hackert, Oliver Strobel, Ingrid Herr
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology and marker expression...
November 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29142746/interaction-between-merkel-cell-carcinoma-and-the-immune-system-pathogenetic-and-therapeutic-implications
#3
Irene Zanetti, Ilaria Coati, Mauro Alaibac
Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma. It usually appears on the face and neck of elderly Caucasian people as a flesh-colored, erythematous or violaceous dome-shaped, non-tender nodule with a smooth surface. In immunocompromised patients with T-cell dysfunction, such as patients with acquired immunodeficiency syndrome (AIDS) or solid organ transplant recipients, the incidence of this disease is markedly increased. This suggests a link between the development of MCC and the immune system...
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29142315/hiv-1-counteracts-an-innate-restriction-by-amyloid-precursor-protein-resulting-in-neurodegeneration
#4
Qingqing Chai, Vladimir Jovasevic, Viacheslav Malikov, Yosef Sabo, Scott Morham, Derek Walsh, Mojgan H Naghavi
While beta-amyloid (Aβ), a classic hallmark of Alzheimer's disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141633/genome-modification-of-cxcr4-by-staphylococcus-aureus-cas9-renders-cells-resistance-to-hiv-1-infection
#5
Qiankun Wang, Shuliang Chen, Qiaoqiao Xiao, Zhepeng Liu, Shuai Liu, Panpan Hou, Li Zhou, Wei Hou, Wenzhe Ho, Chunmei Li, Li Wu, Deyin Guo
BACKGROUND: The CRISPR/Cas9 system has been widely used for genome editing in mammalian cells. CXCR4 is a co-receptor for human immunodeficiency virus type 1 (HIV-1) entry, and loss of CXCR4 function can protect cells from CXCR4 (X4)-tropic HIV-1 infection, making CXCR4 an important target for HIV-1 gene therapy. However, the large size of the CRISPR/SpCas9 system presents an obstacle to its efficient delivery into primary CD4(+) T cells. Recently, a small Staphylococcus aureus Cas9 (SaCas9) has been developed as a genome editing tool can address this question...
November 15, 2017: Retrovirology
https://www.readbyqxmd.com/read/29140551/b-cell-receptor-repertoire-sequencing-in-patients-with-primary-immunodeficiency-a-review
#6
REVIEW
Marie Ghraichy, Jacob D Galson, Dominic F Kelly, Johannes Trück
The advent of next-generation sequencing now allows a detailed assessment of the adaptive immune system in health and disease. In particular, high-throughput B-cell receptor (BCR) repertoire sequencing provides detailed information about the functionality and abnormalities of the B-cell system. However, it is mostly unknown how the BCR repertoire is altered in the context of primary immunodeficiencies (PID) and whether findings are consistent across phenotypes and genotypes. We have performed an extensive literature search of the published work on BCR repertoire sequencing in PID patients, including several forms of predominantly antibody disorders and combined immunodeficiencies...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29138951/chronic-diarrhea-in-common-variable-immunodeficiency-a-case-series-and-review-of-the-literature
#7
Antonio Pecoraro, Liliana Nappi, Ludovica Crescenzi, Francesco P D'Armiento, Arturo Genovese, Giuseppe Spadaro
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition...
November 14, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29137234/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#8
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#9
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135747/experiences-of-hiv-infected-adults-and-healthcare-providers-with-healthcare-delivery-practices-influencing-engagement-in-primary-healthcare-settings-a-qualitative-systematic-review-protocol
#10
Andrea Norberg, John Nelson, Cheryl Holly, Sarah T Jewell, Susan Salmond
The objective of this qualitative systematic review is to examine the experience and impact of health care delivery on health care engagement for adults infected with the human immunodeficiency virus receiving primary care. This review will identify and synthesize the best available evidence on health care structures, processes and practices that promote patient engagement in primary health care.The review question to be addressed is: What are the experiences of people living with human immunodeficiency virus (PLWH) and their health care providers with health care delivery processes and practices that impact engagement in primary health care settings (clinics, physician offices, and other community-based health care settings)? Specifically this review will compile evidence to illuminate health care system structures, provider practices, care delivery and programmatic processes that impact engagement in primary health care, as perceived by PLWH and their providers...
November 2017: JBI Database of Systematic Reviews and Implementation Reports
https://www.readbyqxmd.com/read/29135582/hiv-is-associated-with-airway-obstruction-a-matched-controlled-study
#11
Alain Makinson, Maurice Hayot, Sabrina Eymard-Duvernay, Céline Ribet, François Raffi, Gilles Pialoux, David Zucman, Isabelle Poizot-Martin, Fabrice Bonnet, Sophie Abgrall, Pierre Tattevin, Antoine Cheret, Tristan Ferry, Jean-Marc Mauboussin, Lucie Marchand, Claire Rouzaud, Jacques Reynes, Marie Zins, Vincent Le Moing
OBJECTIVE: to explore whether airway obstruction (AO) is associated with HIV in a cohort of HIV-infected and uninfected smokers. METHODS: People living with HIV (PLWHIV) participated in the ANRS EP48 HIV CHEST study, an early lung cancer diagnosis study with low dose Chest Tomography. HIV-uninfected subjects were from the CONSTANCES cohort. Inclusion criteria were an age > 40 years, a smoking history ≥20 pack-years, and for PLWHIV, a CD4 T-lymphocyte nadir < 350/μl and last CD4 cell count > 100 cells/μl...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29135572/long-term-observational-studies-of-chronic-granulomatous-disease
#12
Maria Kanariou, Kleopatra Spanou, Sofia Tantou
PURPOSE OF REVIEW: Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients...
November 10, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29133261/dual-inhibition-of-brd4-and-pi3k-by-sf2523-suppresses-human-prostate-cancer-cell-growth-in-vitro-and-in-vivo
#13
Gang Shen, Minjun Jiang, Jinxian Pu
Bromodomain-containing protein 4 (BRD4) and phosphatidylinositol 3-kinase (PI3K) are both key oncogenic proteins in human prostate cancer. In the current study, we examined the anti-prostate cancer cell activity by SF2523, a BRD4 and PI3K dual inhibitor. We showed that SF2523 potently inhibited survival and proliferation of the primary human prostate cancer cells. SF2523 induced profound apoptosis activation in prostate cancer cells. The dual inhibitor was yet non-cytotoxic to the prostate epithelial cells...
November 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29132380/addressing-challenges-in-scaling-up-tb-and-hiv-treatment-integration-in-rural-primary-healthcare-clinics-in-south-africa-suthi-a-cluster-randomized-controlled-trial-protocol
#14
Kogieleum Naidoo, Santhanalakshmi Gengiah, Nonhlanhla Yende-Zuma, Nesri Padayatchi, Pierre Barker, Andrew Nunn, Priashni Subrayen, Salim S Abdool Karim
BACKGROUND: A large and compelling clinical evidence base has shown that integrated TB and HIV services leads to reduction in human immunodeficiency virus (HIV)- and tuberculosis (TB)-associated mortality and morbidity. Despite official policies and guidelines recommending TB and HIV care integration, its poor implementation has resulted in TB and HIV remaining the commonest causes of death in several countries in sub-Saharan Africa, including South Africa. This study aims to reduce mortality due to TB-HIV co-infection through a quality improvement strategy for scaling up of TB and HIV treatment integration in rural primary healthcare clinics in South Africa...
November 13, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/29129708/efficacy-of-hepatitis-b-virus-ribonuclease-h-inhibitors-a-new-class-of-replication-antagonists-in-frg-human-liver-chimeric-mice
#15
Kelly R Long, Elena Lomonosova, Qilan Li, Nathan L Ponzar, Juan A Villa, Erin Touchette, Stephen Rapp, R Matt Liley, Ryan P Murelli, Alexandre Grigoryan, R Mark Buller, Lisa Wilson, John Bial, John E Sagartz, John E Tavis
Chronic hepatitis B virus infection cannot be cured by current therapies, so new treatments are urgently needed. We recently identified novel inhibitors of the hepatitis B virus ribonuclease H that suppress viral replication in cell culture. Here, we employed immunodeficient FRG KO mice whose livers had been engrafted with primary human hepatocytes to ask whether ribonuclease H inhibitors can suppress hepatitis B virus replication in vivo. Humanized FRG KO mice infected with hepatitis B virus were treated for two weeks with the ribonuclease H inhibitors #110, an α-hydroxytropolone, and #208, an N-hydroxypyridinedione...
November 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29128761/inborn-errors-of-immunity-underlying-fungal-diseases-in-otherwise-healthy-individuals
#16
REVIEW
Juan Li, Donald C Vinh, Jean-Laurent Casanova, Anne Puel
It has been estimated that there are at least 1.5 million fungal species, mostly present in the environment, but only a few of these fungi cause human disease. Most fungal diseases are self-healing and benign, but some are chronic or life-threatening. Acquired and inherited defects of immunity, including breaches of mucocutaneous barriers and circulating leukocyte deficiencies, account for most severe modern-day mycoses. Other types of infection typically accompany these fungal infections. More rarely, severe fungal diseases can strike otherwise healthy individuals...
November 9, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29128075/flow-cytometric-evaluation-of-primary-immunodeficiencies
#17
REVIEW
Andreas Boldt, Michael Bitar, Ulrich Sack
Primary immunodeficiency diseases are genetic disorders that mostly cause susceptibility to infections and are sometimes associated with autoimmune and malignant diseases. For early detection and management of these diseases, flow cytometric procedures allow an encompassing assessment of cellular phenotypes and cellular functions. State-of-the art cytometry is based today on 8- to 10-color staining and includes an assessment of lineage maturation and functional markers.
December 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29127275/allogeneic-stem-cell-transplantation-in-fully-mhc-matched-mauritian-cynomolgus-macaques-recapitulates-diverse-human-clinical-outcomes
#18
Benjamin J Burwitz, Helen L Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W Legasse, Katherine B Hammond, Stephanie L Junell, Jason S Reed, Benjamin N Bimber, Justin M Greene, Gabriela M Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K Axthelm, Rebecca Ducore, Anne Lewis, Lois M A Colgin, Theodore Hobbs, Lauren D Martin, Betsy Ferguson, Charles R Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J Stanton, Richard T Maziarz, Jonah B Sacha
Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.-tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29126302/the-clinical-utility-of-measuring-igg-subclass-immunoglobulins-during-immunological-investigation-for-suspected-primary-antibody-deficiencies
#19
Antony R Parker, Markus Skold, David B Ramsden, J Gonzalo Ocejo-Vinyals, Marcos López-Hoyos, Stephen Harding
Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29123518/human-primary-macrophages-derived-in-vitro-from-circulating-monocytes-comprise-adherent-and-non-adherent-subsets-with-differential-expression-of-siglec-1-and-cd4-and-permissiveness-to-hiv-1-infection
#20
Ousman Jobe, Jiae Kim, Eric Tycksen, Sayali Onkar, Nelson L Michael, Carl R Alving, Mangala Rao
Macrophages are a major target for human immunodeficiency virus type 1 (HIV-1) infection. However, macrophages are largely heterogeneous and may exhibit differences in permissiveness to HIV-1 infection. This study highlights the interplay of macrophage heterogeneity in HIV-1 pathogenesis. We show that monocyte-derived macrophages (MDMs) could be divided into two distinct subsets: CD14(+)Siglec-1(hi)CD4(+) (non-adherent MDM) and CD14(+)Siglec-1(Lo)CD4(-) (adherent MDM). The CD14(+)Siglec-1(hi)CD4(+)MDM subset represented the smaller proportion in the macrophage pool, and varied among different donors...
2017: Frontiers in Immunology
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