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https://www.readbyqxmd.com/read/28319462/late-effects-of-exposure-to-ionizing-radiation-and-age-on-human-thymus-morphology-and-function
#1
Reiko Ito, Laura P Hale, Susan M Geyer, Jie Li, Andrew Sornborger, Junko Kajimura, Yoichiro Kusunoki, Kengo Yoshida, Marcel R M van den Brink, Seishi Kyoizumi, Nancy R Manley, Kei Nakachi, Gregory D Sempowski
The thymus is essential for proper development and maintenance of a T-cell repertoire that can respond to newly encountered antigens, but its function can be adversely affected by internal factors such as pregnancy and normal aging or by external stimuli such as stress, infection, chemotherapy and ionizing radiation. We have utilized a unique archive of thymus tissues, obtained from 165 individuals, exposed to the 1945 atomic bomb blast in Hiroshima, to study the long-term effects of receiving up to ∼3 Gy dose of ionizing radiation on human thymus function...
March 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/28318109/agreement-between-factor-xiii-activity-and-antigen-assays-in-measurement-of-factor-xiii-a-french-multicenter-study-of-147-human-plasma-samples
#2
C Caron, R Meley, V Le Cam Duchez, M F Aillaud, C Lavenu-Bombled, F Dutrillaux, C Flaujac, A Ryman, C Ternisien, D Lasne, H Galinat, C Pouplard
INTRODUCTION: Factor XIII (FXIII) deficiency is a rare hemorrhagic disorder whose early diagnosis is crucial for appropriate treatment and prophylactic supplementation in cases of severe deficiency. International guidelines recommend a quantitative FXIII activity assay as first-line screening test. FXIII antigen measurement may be performed to establish the subtype of FXIII deficiency (FXIIID) when activity is decreased. METHODS: The aim of this multicenter study was to evaluate the analytical and diagnostic levels of performance of a new latex immunoassay, K-Assay(®) FXIII reagent from Stago, for first-line measurement of FXIII antigen...
March 20, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28317992/synthetic-glycoconjugates-characterize-the-fine-specificity-of-brucella-a-and-m-monoclonal-antibodies
#3
Satadru Sekhar Mandal, N Vijaya Ganesh, Joanna M Sadowska, David R Bundle
The dominant cell wall antigen of Brucella bacteria is the O-polysaccharide component of the smooth lipopolysaccharide. Infection by various Brucella biovars causes abortions and infertility in a wide range of domestic and wild animals and debilitating disease in humans. Diagnosis relies on the detection of antibodies to the A and M antigens expressed in the O-polysaccharide. This molecule is a homopolymer of the rare monosaccharide, 4-formamido-4,6-dideoxy-d-mannopyranose (Rha4NFo). The A epitope is created by a uniform α1,2 linked internal polymeric sequence capped by a distinct tetrasaccharide sequence defining the M antigen...
March 20, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28306188/protein-modelling-to-understand-fgb-mutations-leading-to-congenital-hypofibrinogenaemia
#4
A Casini, R Vilar, Y Beauverd, D Aslan, K Devreese, V Mondelaers, L Alberio, C Gubert, P de Moerloose, M Neerman-Arbez
INTRODUCTION: Congenital hypofibrinogenaemia is a quantitative fibrinogen disorder characterized by proportionally decreased levels of functional and antigenic fibrinogen. Mutations accounting for quantitative fibrinogen disorders are relatively frequent in the conserved COOH-terminal globular domains of the γ and Bβ chains. The latter mutations are of particular interest since the Bβ-chain is considered the rate-limiting chain in the hepatic production of the fibrinogen hexamer. AIM: The aim of this study was to study the molecular pattern of four patients with congenital hypofibrinogenaemia...
March 17, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#5
Carolina Purroy, Robert L Fairchild, Toshiaki Tanaka, William M Baldwin, Joaquin Manrique, Joren C Madsen, Robert B Colvin, Alessandro Alessandrini, Bruce R Blazar, Miguel Fribourg, Chiara Donadei, Umberto Maggiore, Peter S Heeger, Paolo Cravedi
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4(+) T cells into functional Foxp3(+) regulatory T cells (Treg)...
March 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28296717/abdominal-wall-allograft-preclinical-biomechanical-investigation-of-a-novel-reconstructive-adjunct
#6
Brent R DeGeorge, Jonathan Bryce Olenczak, Angela Pineros-Fernandez, Raymond F Morgan, Patrick S Cottler, David B Drake
INTRODUCTION: Acellular dermal matrices have revolutionized abdominal wall reconstruction; however, device failure and hernia recurrence remain significant problems. Fascia grafts are a reconstructive adjunct with increased tensile strength compared with acellular dermal matrices; however, clinical use is limited by insufficient donor material and donor site morbidity. To this end, we investigate the biomechanical properties of human abdominal wall allografts (AWAs) consisting of the anterior rectus sheath from xiphoid to pubis...
March 14, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28295360/human-platelet-antigen-antibody-induction-in-uncomplicated-pregnancy-is-associated-with-hla-sensitization
#7
Viktoria S A Reiher, Gideon Hönger, Laura Infanti, Jakob R Passweg, Irene Hösli, Beat M Frey, Christoph Gassner, Stefan Meyer, Andreas S Buser, Andreas Holbro, Stefan Schaub
BACKGROUND: Alloimmunization against human platelet antigens (HPAs) during pregnancy is rare but can lead to severe bleeding disorders, such as fetal and neonatal alloimmune thrombocytopenia. STUDY DESIGN AND METHODS: In a cohort of 241 uncomplicated pregnancies, we investigated the immunogenicity of HPA mismatches and correlated HLA sensitization with HPA antibody formation. HPA antibodies were measured with a Luminex-based multiplex assay. RESULTS: HPA mismatches were observed in 109 of 241 pregnancies (45%), but child-specific HPA antibodies were only found in two of 109 cases (2%), indicating a low immunogenicity...
March 10, 2017: Transfusion
https://www.readbyqxmd.com/read/28292985/binding-of-candida-albicans-to-human-ceacam1-and-ceacam6-modulates-the-inflammatory-response-of-intestinal-epithelial-cells
#8
Esther Klaile, Mario M Müller, Miriam R Schäfer, Ann-Katrin Clauder, Sabina Feer, Kerstin A Heyl, Magdalena Stock, Tilman E Klassert, Peter F Zipfel, Bernhard B Singer, Hortense Slevogt
Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM5 (CEA), and CEACAM6 (CD66c) are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans) also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28289713/th17-cells-are-refractory-to-senescence-and-retain-robust-antitumor-activity-after-long-term-ex-vivo-expansion
#9
Jacob S Bowers, Michelle H Nelson, Kinga Majchrzak, Stefanie R Bailey, Baerbel Rohrer, Andrew D M Kaiser, Carl Atkinson, Luca Gattinoni, Chrystal M Paulos
Adoptive immunotherapy for solid tumors relies on infusing large numbers of T cells to mediate successful antitumor responses in patients. While long-term rapid-expansion protocols (REPs) produce sufficient numbers of CD8(+) T cells for treatment, they also cause decline in the cell's therapeutic fitness. In contrast, we discovered that IL-17-producing CD4(+) T cells (Th17 cells) do not require REPs to expand 5,000-fold over 3 weeks. Also, unlike Th1 cells, Th17 cells do not exhibit hallmarks of senescence or apoptosis, retaining robust antitumor efficacy in vivo...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28284256/novel-interferon-gamma-assays-for-diagnosing-tuberculosis-in-young-children-in-india
#10
N Shaikh, A Gupte, S Dharmshale, S Pokkali, M Thakar, V J Upadhye, A A Ordonez, A Kinikar, N Gupte, V Mave, A Kagal, A Gupta, A Lalvani, R Paranjpe, R Bharadwaj, S K Jain
SETTING: The tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used as supportive evidence to diagnose active tuberculosis (TB). Novel IGRAs could improve diagnosis, but data are lacking in young children. DESIGN: Children (age 5 years) with suspected TB were prospectively screened at a tertiary hospital in Pune, India; the children underwent TST, and standard (early secretory antigenic target 6 and culture filtrate protein 10) and enhanced (five additional novel antigens) enzyme-linked immunospot (ELISpot) assays...
April 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28281872/novel-anti-sialyl-tn-monoclonal-antibodies-and-antibody-drug-conjugates-demonstrate-tumor-specificity-and-anti-tumor-activity
#11
Jillian M Prendergast, Ana Paula Galvao da Silva, David A Eavarone, Darius Ghaderi, Mai Zhang, Dane Brady, Joan Wicks, Julie DeSander, Jeff Behrens, Bo R Rueda
Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins...
February 22, 2017: MAbs
https://www.readbyqxmd.com/read/28280265/effect-of-blood-type-on-anti-%C3%AE-gal-immunity-and-the-incidence-of-infectious-diseases
#12
Alejandro Cabezas-Cruz, Lourdes Mateos-Hernández, Pilar Alberdi, Margarita Villar, Gilles Riveau, Emmanuel Hermann, Anne-Marie Schacht, Jamal Khalife, Margarida Correia-Neves, Christian Gortazar, José de la Fuente
The identification of factors affecting the susceptibility to infectious diseases is essential toward reducing their burden on the human population. The ABO blood type correlates with susceptibility to malaria and other infectious diseases. Due to the structural similarity between blood antigen B and Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), we hypothesized that self-tolerance to antigen B affects the immune response to α-Gal, which in turn affects the susceptibility to infectious diseases caused by pathogens carrying α-Gal on their surface...
March 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28279591/hla-g-at-the-interface-of-maternal-fetal-tolerance
#13
REVIEW
Leonardo M R Ferreira, Torsten B Meissner, Tamara Tilburgs, Jack L Strominger
During pregnancy, semiallogeneic fetal extravillous trophoblasts (EVT) invade the uterine mucosa without being rejected by the maternal immune system. Several mechanisms were initially proposed by Peter Medawar half a century ago to explain this apparent violation of the laws of transplantation. Then, three decades ago, an unusual human leukocyte antigen (HLA) molecule was identified: HLA-G. Uniquely expressed in EVT, HLA-G has since become the center of the present understanding of fetus-induced immune tolerance...
March 6, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28278336/human-leukocyte-antigen-class-i-genes-associated-with-stevens-johnson-syndrome-and-severe-ocular-complications-following-use-of-cold-medicine-in-a-brazilian-population
#14
Tais H Wakamatsu, Mayumi Ueta, Katsushi Tokunaga, Yukinori Okada, Renata R Loureiro, Karita A Costa, Juliana Maria F Sallum, José Arthur Milhomens, Chikara Inoue, Chie Sotozono, José Álvaro P Gomes, Shigeru Kinoshita
Importance: Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs). Objective: To investigate the association between HLA class I genes and cold medicine (CM)-associated SJS/TEN with SOCs. Design, Setting, and Participants: This case-control study was conducted between February 8, 2013, and August 29, 2014...
March 9, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28272405/parp1-promotes-gene-expression-at-the-post-transcriptiona-level-by-modulating-the-rna-binding-protein-hur
#15
Yueshuang Ke, Yanlong Han, Xiaolan Guo, Jitao Wen, Ke Wang, Xue Jiang, Xue Tian, Xueqing Ba, Istvan Boldogh, Xianlu Zeng
Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28272393/experimental-vaccine-induces-th1-driven-immune-responses-and-resistance-to-neisseria-gonorrhoeae-infection-in-a-murine-model
#16
Y Liu, L A Hammer, W Liu, M M Hobbs, R A Zielke, A E Sikora, A E Jerse, N K Egilmez, M W Russell
Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMVs) plus microencapsulated interleukin-12 (IL-12), and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10-13 days, those immunized with OMV plus IL-12 cleared infection with homologous gonococcal strains in 6-9 days. Significant protection was also seen after challenge with antigenically distinct strains of N. gonorrhoeae, and protective anamnestic immunity persisted for at least 6 months after immunization...
March 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28270598/sensing-of-cell-stress-by-human-%C3%AE-%C3%AE-tcr-dependent-recognition-of-annexin-a2
#17
Romain Marlin, Angela Pappalardo, Hannah Kaminski, Carrie R Willcox, Vincent Pitard, Sonia Netzer, Camille Khairallah, Anne-Marie Lomenech, Christelle Harly, Marc Bonneville, Jean-François Moreau, Emmanuel Scotet, Benjamin E Willcox, Benjamin Faustin, Julie Déchanet-Merville
Human γδ T cells comprise a first line of defense through T-cell receptor (TCR) recognition of stressed cells. However, the molecular determinants and stress pathways involved in this recognition are largely unknown. Here we show that exposure of tumor cells to various stress situations led to tumor cell recognition by a Vγ8Vδ3 TCR. Using a strategy that we previously developed to identify antigenic ligands of γδ TCRs, annexin A2 was identified as the direct ligand of Vγ8Vδ3 TCR, and was found to be expressed on tumor cells upon the stress situations tested in a reactive oxygen species-dependent manner...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28264647/the-repertoire-dissimilarity-index-as-a-method-to-compare-lymphocyte-receptor-repertoires
#18
Christopher R Bolen, Florian Rubelt, Jason A Vander Heiden, Mark M Davis
BACKGROUND: The B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking. RESULTS: In this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization...
March 7, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28263308/autoimmunity-against-a-defective-ribosomal-insulin-gene-product-in-type-1-diabetes
#19
Maria J L Kracht, Menno van Lummel, Tatjana Nikolic, Antoinette M Joosten, Sandra Laban, Arno R van der Slik, Peter A van Veelen, Françoise Carlotti, Eelco J P de Koning, Rob C Hoeben, Arnaud Zaldumbide, Bart O Roep
Identification of epitopes that are recognized by diabetogenic T cells and cause selective beta cell destruction in type 1 diabetes (T1D) has focused on peptides originating from native beta cell proteins. Translational errors represent a major potential source of antigenic peptides to which central immune tolerance is lacking. Here, we describe an alternative open reading frame within human insulin mRNA encoding a highly immunogenic polypeptide that is targeted by T cells in T1D patients. We show that cytotoxic T cells directed against the N-terminal peptide of this nonconventional product are present in the circulation of individuals diagnosed with T1D, and we provide direct evidence that such CD8(+) T cells are capable of killing human beta cells and thereby may be diabetogenic...
February 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#20
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
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