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Federico Carlini, Virginia Ferreira, Stéphane Buhler, Audrey Tous, Jean-François Eliaou, Céline René, Jacques Chiaroni, Christophe Picard, Julie Di Cristofaro
The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors...
2016: PloS One
Aura Burian, Kevin L Wang, Kathryn A K Finton, Ni Lee, Akiko Ishitani, Roland K Strong, Daniel E Geraghty
Based on previous findings supporting HLA-F as a ligand for KIR3DL2 and KIR2DS4, we investigated the potential for MHC-I open conformers (OCs) as ligands for KIR3DS1 and KIR3DL1 through interactions measured by surface plasmon resonance. These measurements showed physical binding of KIR3DS1 but not KIR3DL1 with HLA-F and other MHC-I OC while also confirming the allotype specific binding of KIR3DL1 with MHC-I peptide complex. Concordant results were obtained with biochemical pull-down from cell lines and biochemical heterodimerization experiments with recombinant proteins...
2016: PloS One
Chao Wu, Ye Liu, Xiangxiang Gu, Tianhui Zhu, Shuang Yang, Wei Sun
In eukaryotic cells, the post-translational modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is the most common trigger for protein degradation and is involved in the regulation of a wide range of biological processes. FAT10 (HLA-F-adjacent transcript 10), which belongs to the UBL family, is activated specifically through the UBA6-USE1 cascade and targets substrates covalently for 26S proteasomal degradation. LMO2 is a well-recognized transcriptional regulator in hematopoietic and endothelial systems; however, it is predominantly located in the cytoplasm of epithelium-derived cells...
September 23, 2016: Biochemical and Biophysical Research Communications
Sarah J Richardson, Teresa Rodriguez-Calvo, Ivan C Gerling, Clayton E Mathews, John S Kaddis, Mark A Russell, Marie Zeissler, Pia Leete, Lars Krogvold, Knut Dahl-Jørgensen, Matthias von Herrath, Alberto Pugliese, Mark A Atkinson, Noel G Morgan
AIMS/HYPOTHESIS: Human pancreatic beta cells may be complicit in their own demise in type 1 diabetes, but how this occurs remains unclear. One potentially contributing factor is hyperexpression of HLA class I antigens. This was first described approximately 30 years ago, but has never been fully characterised and was recently challenged as artefactual. Therefore, we investigated HLA class I expression at the protein and RNA levels in pancreases from three cohorts of patients with type 1 diabetes...
November 2016: Diabetologia
Wilfredo F Garcia-Beltran, Angelique Hölzemer, Gloria Martrus, Amy W Chung, Yovana Pacheco, Camille R Simoneau, Marijana Rucevic, Pedro A Lamothe-Molina, Thomas Pertel, Tae-Eun Kim, Haley Dugan, Galit Alter, Julie Dechanet-Merville, Stephanie Jost, Mary Carrington, Marcus Altfeld
The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro...
September 2016: Nature Immunology
Thálitta Hetamaro Ayala Lima, Renato Vidal Buttura, Eduardo Antônio Donadi, Luciana Caricati Veiga-Castelli, Celso Teixeira Mendes-Junior, Erick C Castelli
Human Leucocyte Antigen F (HLA-F) is a non-classical HLA class I gene distinguished from its classical counterparts by low allelic polymorphism and distinctive expression patterns. Its exact function remains unknown. It is believed that HLA-F has tolerogenic and immune modulatory properties. Currently, there is little information regarding the HLA-F allelic variation among human populations and the available studies have evaluated only a fraction of the HLA-F gene segment and/or have searched for known alleles only...
October 2016: Human Immunology
Courtney K Burrows, Gülüm Kosova, Catherine Herman, Kristen Patterson, Katherine E Hartmann, Digna R Velez Edwards, Mary D Stephenson, Vincent J Lynch, Carole Ober
Fertility traits in humans are heritable, however, little is known about the genes that influence reproductive outcomes or the genetic variants that contribute to differences in these traits between individuals, particularly women. To address this gap in knowledge, we performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium. We identified 423 cis-eQTLs for 132 genes that were significant at a false discovery rate (FDR) of 1%...
July 2016: PLoS Genetics
SungWon Song, Carlos J Miranda, Lyndsey Braun, Kathrin Meyer, Ashley E Frakes, Laura Ferraiuolo, Shibi Likhite, Adam K Bevan, Kevin D Foust, Michael J McConnell, Christopher M Walker, Brian K Kaspar
Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non-cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death...
April 2016: Nature Medicine
Ines Zidi, Najla Kharrat, Rania Abdelhedi, Amna Ben Hassine, Ahmed Baligh Laaribi, Hamza Ben Yahia, Nouha Bouayed Abdelmoula, Leila Abid, Ahmed Rebai, Roberta Rizzo
AIMS: Several evidences suggest the association between the evolution of coronary artery disease (CAD) and the development of coronary syndrome that is often associated with disrupted plaque and partial or complete thrombosis of the related artery. Because of the inflammatory nature of CAD, we investigated the human leukocyte antigen (HLA)-G, HLA-E, and HLA-F genetic polymorphisms within CAD patients and evaluated their potential association with this disease in Tunisian population. METHODS: Different polymorphisms in HLA-G (14-bp Insertion/Deletion, +3142C/G), HLA-E (HLA-E*01:01/01:03 A/G), HLA-F (HLA-F*01:02 T/C, 01:03 C/T, 01:04 A/C) genes were typed using different laboratory techniques in a cohort of 89 CAD patients and 84 controls...
April 2016: Human Immunology
V Jucaud, M H Ravindranath, P I Terasaki, L E Morales-Buenrostro, F Hiepe, T Rose, R Biesen
T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over-expression of human leucocyte antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and β2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex(®)-based flow cytometry...
March 2016: Clinical and Experimental Immunology
N M Suraeva, L F Morozova, A V Samoilov, O S Burova, V A Golubeva, M A Baryshnikova, A Yu Baryshnikov
Exposure of Mel Ibr human melanoma cells to chicken embryo extract resulted in the appearance of a subclone with morphological and growth characteristics similar to those of embryonic stem cells. The subclone differed from the parental line cells by a sharply reduced percentage of HLA-DR(+) and CD54(+) cells, a significantly elevated percentage of CD63(+) cells, and appearance of CD133(+) and Oct-4A(+) cells. Hence, the subclone cells were characterized by the same features as stem tumor cells and could be responsible for further progress of tumor growth...
August 2015: Bulletin of Experimental Biology and Medicine
W Zhang, Y He, W Wang, Z Han, J He, N Chen, L Dong, S Tao, J He, F Zhu, H Lv
The DNA-based method is used widely for HLA genotyping in routine work, but some allele may be dropout in the genotyping procedure. Here, we reported a case with HLA-A allele dropout in the Sanger PCR-SBT test. The initial PCR-SBT method with a commercial agent kit was not characterized, and the result of Luminex technology indicated the dropout as a HLA-A*02 allele. Subsequently, the sequences of exons 2-4 were fully matched with the A*02:07 and A*11:01:01 by allele group-specific primer amplification PCR-SBT...
December 2015: International Journal of Immunogenetics
Ian Nivison-Smith, Peter Bardy, Anthony J Dodds, David D F Ma, Donna Aarons, Steven Tran, Leonie Wilcox, Jeff Szer
This report describes hematopoietic cell transplantation (HCT) activity and outcome in Australia and New Zealand during the years 2005 to 2013. In 2013, 1018 autologous, 221 allogeneic with related donors, and 264 allogeneic with unrelated donors HCT were performed in 40 centers in Australia, with corresponding figures of 147, 39, and 47 in 6 centers in New Zealand. Annual numbers of HCT in 2013 increased, compared to 2005, by 25% in Australia and by 52% in New Zealand. The majority of both allogeneic and autologous HCT used peripheral blood as the stem cell source for all years studied...
February 2016: Biology of Blood and Marrow Transplantation
Dennis F Habig, Justine L Gaspari, Parvez M Lokhandwala, Ronald E Domen, Catherine S Abendroth, Zakiyah Kadry, Nasrollah Ghahramani, Riaz Ali Shah, Ashokkumar Jain, Hiroko Shike
The majority of de novo donor specific HLA antibodies (DSAs) in transplant patients are directed to HLA-DQ antigens, which consist of a heterodimer of alpha and beta chains. Although a heterodimer can theoretically be cis- or trans-encoded, the sensitizing forms generally appear to be forms. DSA to DQ trans-heterodimer has never been reported. We reviewed 360 post-kidney transplant recipients (transplant: 2002-2013; follow-up: 5.6±3.3years). DQ DSA was detected in 46 of 57 patients who developed DSA. DSA specificity was consistent with donor mismatched DQ trans-heterodimers in three patients: DQ2...
August 2015: Human Immunology
Eva Distler, Jana Albrecht, Ariane Brunk, Shamsul Khan, Elke Schnürer, Michaela Frey, Anja Mottok, Ana-Laura Jordán-Garrote, Christian Brede, Andreas Beilhack, Andreas Mades, Dirk Tomsitz, Matthias Theobald, Wolfgang Herr, Udo F Hartwig
Adoptive transfer of donor-derived cytolytic T-lymphocytes (CTL) has evolved as a promising strategy to improve graft-versus-leukemia (GvL) effects in allogeneic hematopoietic stem-cell transplantation. However, durable clinical responses are often hampered by limited capability of transferred T cells to establish effective and sustained antitumor immunity in vivo. We therefore analyzed GvL responses of acute myeloid leukemia (AML)-reactive CD8(+) CTL with central and effector memory phenotype in a new allogeneic donor-patient specific humanized mouse model...
March 1, 2016: International Journal of Cancer. Journal International du Cancer
L Wisgrill, A Spittler, J Hartmann, C Lamm, F Preiing, K Dragosits, A Bee
INTRODUCTION: LPS induced monocyte TNF-α secretion, constitutive interleukin 6 (IL-6) expression and monocyte HLA-DR expression are important monitoring parameters in sepsis and are indicative for clinical outcome. The present study investigated whether these parameters change over time in whole blood samples using different anticoagulants under various temperature conditions. METHODS: EDTA, citrate and heparin anticoagulated whole blood from healthy individuals was processed immediately or stored for up to 48 h at 4°C and 21°C...
October 2015: Shock
F Ren, J Li, X Jiang, K Xiao, D Zhang, Z Zhao, J Ai, C Hou, Y Jia, G Han, L Xie
Immune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim-3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim-3 (sTim-3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim-3 and human leukocyte antigen-DR (HLA-DR) on the circulating monocytes were detected using flow cytometry...
November 2015: Tissue Antigens
A F Zahorchak, M B Ezzelarab, L Lu, H R Turnquist, A W Thomson
Increasing evidence from small animal models shows that myeloid-derived suppressor cells (MDSCs) can play a crucial role in inhibiting allograft rejection and promoting transplant tolerance. We identified CD3(-)CD20(-)HLA-DR(-)CD14(+)CD33(+)CD11b(+) cells in peripheral blood of healthy rhesus macaques. These putative monocytic MDSCs constituted 2.1% ± 1.7% of lin(-)HLA-DR(-) peripheral blood mononuclear cells. Administration of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF increased their incidence to 5...
February 2016: American Journal of Transplantation
R Peffault de Latour, M Labopin, J Cornelissen, S Vigouroux, C Craddock, D Blaise, A Huyn, L Vindelov, J Maertens, P Chevallier, N Fegueux, G Socié, J Y Cahn, E Petersen, H Schouten, B Lioure, N Russell, L L Corral, F Ciceri, A Nagler, M Mohty
Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010)...
November 2015: Bone Marrow Transplantation
N Kröger, M Bornhäuser, M Stelljes, U Pichlmeier, R Trenschel, C Schmid, R Arnold, H Martin, M Heinzelmann, C Wolschke, R G Meyer, W Bethge, G Kobbe, F Ayuk, N Gökbuget, D Hölzer, A Zander, D Beelen
TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated...
December 2015: Bone Marrow Transplantation
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