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https://www.readbyqxmd.com/read/28817402/the-importance-of-natural-killer-cell-killer-immunoglobulin-like-receptor-mismatch-in-transplant-outcomes
#1
Kate Stringaris, Austin J Barrett
PURPOSE OF REVIEW: In recent years, the rules of engagement between natural killer (NK) cells and their targets have become better defined with the identification of an array of NK surface molecules, notably the killer immunoglobulin-like (KIR) receptors and their ligands on target cells through which signals of activation or suppression of NK function are mediated. After allogeneic stem cell transplantation (SCT), the opportunity for NK cell activation can occur both in human leucocyte antigen (HLA) matched and HLA mismatched pairs...
August 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28812990/human-leukocyte-antigen-c-12-02-02-and-killer-immunoglobulin-like-receptor-2dl5-are-distinctly-associated-with-ankylosing-spondylitis-in-the-taiwanese
#2
Chin-Man Wang, Sheng-Hung Wang, Yeong-Jian Jan Wu, Jing-Chi Lin, Jianming Wu, Ji-Yih Chen
Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28811973/nk-cell-dysfunction-in-chronic-lymphocytic-leukemia-is-associated-with-loss-of-the-mature-cells-expressing-inhibitory-killer-cell-ig-like-receptors
#3
Alexander W MacFarlane, Mowafaq Jillab, Mitchell R Smith, R Katherine Alpaugh, Marion E Cole, Samuel Litwin, Michael M Millenson, Tahseen Al-Saleem, Adam D Cohen, Kerry S Campbell
A prospective analysis of natural killer (NK) cell phenotype and function was performed on fresh peripheral blood samples from untreated patients with B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Compared to healthy controls, CD56(dim) NK cells in CLL patients displayed reduced expression of the NKG2D activating receptor and increased CD27 expression, which indicates declines in mature cells. In addition, NK cells from CLL patients showed reduced degranulation responses toward transformed B cells alone or with rituximab and were more sensitive to activation-induced cell death...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810810/reduced-expression-of-siglec-7-nkg2a-and-cd57-on-terminally-differentiated-cd56-cd16-nk-cell-subset-is-associated-with-nk-cell-dysfunction-in-chronic-hiv-1-clade-c-infection
#4
Michael Zulu, Kewreshini Naidoo, Zenele Mncube, Manjeetha Jaggernath, Philip Jr Goulder, Thumbi Ndung'u, Marcus Altfeld, Christina Fanesa Thobakgale
BACKGROUND: HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. METHODS: NK cell phenotypic profiles were characterized by assessing Siglec-7, NKG2A and NKG2C markers on frozen peripheral blood mononuclear cells (PBMCs) from viremic, antiretroviral therapy (ART)-naïve HIV-1 chronically infected participants (n=23), HIV-1 chronically infected participants who have been on combination antiretroviral therapy (cART) for at least 12 months (n=23) compared to healthy donors (n=23)...
August 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#5
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28804970/arrhythmogenic-gene-remodelling-in-elderly-patients-with-type-2-diabetes-with-aortic-stenosis-and-normal-left-ventricular-ejection-fraction
#6
R Ashrafi, P Modi, A Y Oo, D M Pullan, K Jian, H Zhang, J Yanni Gerges, G Hart, M R Boyett, G K Davis, J P H Wilding
Type 2 diabetes is associated with higher rate of ventricular arrhythmias and this is hypothesised to be independent of coronary artery disease or hypertension. To investigate further we compared changes in left ventricular myocardial gene expression in Type 2 diabetes to patients in a control group with left ventricular hypertrophy. 9 control patients and 7 patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal averaged ECGs and echocardiograms prior to surgery...
August 14, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28801811/association-of-variably-expressed-kir3dl1-alleles-with-psoriatic-disease
#7
Jeffrey Berinstein, Remy Pollock, Fawnda Pellett, Arane Thavaneswaran, Vinod Chandran, Dafna D Gladman
The purpose of this study is to examine the genetic interaction of variably expressed killer cell immunoglobulin-like receptor (KIR) 3DL1 alleles with their cognate ligand, human leukocyte antigen (HLA)-Bw4, in susceptibility to psoriatic disease (PsD). A novel allelic typing system was developed to differentiate KIR3DL1 alleles (*High, *Low, *Null expression, and 3DS1), in PsD patients, including those with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC) and healthy controls. Frequencies of each KIR3DL1 allele, Bw4-80I and Bw4-80T, as well as the genetic interaction between the KIR3DL1 alleles and the Bw4 epitope were analyzed...
August 11, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28796561/kir-channels-mediate-vasodilation-but-not-sympatholysis
#8
Christopher M Hearon, Frank A Dinenno
No abstract text is available yet for this article.
August 10, 2017: Channels
https://www.readbyqxmd.com/read/28783683/class-i-hla-haplotypes-form-two-schools-that-educate-nk-cells-in-different-ways
#9
Amir Horowitz, Zakia Djaoud, Neda Nemat-Gorgani, Jeroen Blokhuis, Hugo G Hilton, Vivien Béziat, Karl-Johan Malmberg, Paul J Norman, Lisbeth A Guethlein, Peter Parham
Natural killer (NK) cells are lymphocytes that have vital functions in innate and adaptive immunity, as well as placental reproduction. Polymorphic human leukocyte antigen (HLA) class I educates NK cells through interactions with killer cell immunoglobulin-like receptors (KIRs) and by supplying peptides that bind HLA-E to form ligands for CD94/NKG2A receptors on NK cells. HLA-B dimorphism in the leader peptide modulates this latter function: -21methionine (-21M) delivers functional peptides, but -21threonine (-21T) does not...
September 9, 2016: Science Immunology
https://www.readbyqxmd.com/read/28757124/functional-mapping-of-the-n-terminal-arginine-cluster-and-c-terminal-acidic-residues-of-kir6-2-channel-fused-to-a-g-protein-coupled-receptor
#10
Maria A Principalli, Laura Lemel, Anaëlle Rongier, Anne-Claire Godet, Karla Langer, Jean Revilloud, Leonardo Darré, Carmen Domene, Michel Vivaudou, Christophe J Moreau
Ion channel-coupled receptors (ICCRs) are original man-made ligand-gated ion channels created by fusion of G protein-coupled receptors (GPCRs) to the inward-rectifier potassium channel Kir6.2. GPCR conformational changes induced by ligand binding are transduced into electrical current by the ion channel. This functional coupling is closely related to the length of the linker region formed by the GPCR C-terminus (C-ter) and Kir6.2N-terminus (N-ter). Manipulating the GPCR C-ter length allows to finely tune the channel regulation, both in amplitude and sign (opening or closing Kir6...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28755388/kir-on-the-cusp%C3%A2-of%C3%A2-modern-immunogenetics
#11
REVIEW
Francesco Colucci, James Traherne
Killer Immunoglobulin-like Receptors (KIR) and their Human Leukocyte Antigen (HLA) ligands play a central role in immunity and human health. These molecules are encoded by gene families with copy number variation, extreme levels of sequence diversity and complex expression patterns. The rapid evolution of KIR and HLA genes and their associations with infectious diseases, pregnancy disorders, immunopathologies and outcome of cell transplantation has generated considerable interest from immunologists, geneticists and clinicians...
July 29, 2017: Immunology
https://www.readbyqxmd.com/read/28751893/patients-lacking-a-kir-ligand-of-hla-group-c1-or-c2-have-a-better-outcome-after-umbilical-cord-blood-transplantation
#12
Carmen Martínez-Losada, Carmen Martín, Rafael Gonzalez, Bárbara Manzanares, Estefania García-Torres, Concha Herrera
Donor natural killer (NK) cells can destroy residual leukemic cells after allogeneic hematopoietic stem cell transplantation. This effect is based on the interaction of killer-cell immunoglobulin-like receptors (KIR) of donor NK cells with ligands of the major histocompatibility complex found on the surface of the target cells. HLA-C1 subtypes provide the ligand for KIR2DL2 and KIR2DL3 and the HLA-C2 subtypes for KIR2DL1. We have studied the probability of relapse (PR) after single-unit unrelated cord blood transplantation (UCBT) in relation to the potential graft-vs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28747464/lethal-digenic-mutations-in-the-k-channels-kir4-1-kcnj10-and-slack-kcnt1-associated-with-severe-disabling-seizures-and-neurodevelopmental-delay
#13
Sonia Majed Hasan, Ameera Balobaid, Alessandro Grottesi, Omar Dabbagh, Marta Cenciarini, Rifaat Rawashdeh, Afaf Al-Sagheir, Cecilia Bove, Lara Macchioni, Mauro Pessia, Mohammed Al-Owain, Maria Cristina D'Adamo
A 2-year-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia and tonic-clonic seizures that caused the death of the patient. Targeted and whole-exome sequencing revealed two heterozygous missense variants: a novel mutation in KCNJ10 gene that encodes for the inwardly-rectifying K(+) channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na(+)-activated K(+) channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4...
July 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28741475/cachexia-and-brown-fat-a-burning-issue-in-cancer
#14
Serkan Kir, Bruce M Spiegelman
Cachexia, a progressive weight loss in cancer patients that results from tumor-induced energy wasting, is a serious problem that interferes with response to treatment and affects quality of life. Recent studies suggest that thermogenesis of adipose tissues is involved in energy wasting and also point to a link between the atrophy of fat and muscle. Tumor-derived PTHrP has emerged as a key molecule playing multiple roles in cachexia, from fat 'browning' factor to potential therapeutic target.
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28734803/distribution-of-kir-genes-and-kir2ds4-gene-variants-in-two-mexican-mestizo-populations
#15
Machado-Sulbaran Andrea Carolina, Muñoz-Valle José Francisco, Ramírez-Dueñas María Guadalupe, Baños-Hernández Christian Johana, Machuca-Graciano Omar, Velarde-De la Cruz Erandi Enif, Parra-Rojas Isela, Sánchez-Hernández Pedro Ernesto
Killer immunoglobulin-like receptors (KIR) are transmembrane proteins that regulate NK and T cell subsets by recognizing HLA-I molecules as ligands. The KIR gene family consists of 16 genes, located at chromosome 19q13.4. KIR gene frequencies vary among populations. In Mexico, HLA and genetic ancestry studies show that Mestizo populations have different genetic backgrounds based on admixture with European, African, and Asian ancestry. This study aimed to evaluate the frequencies of KIR genes and genotypes in Guerrero and Jalisco, two Mexican Mestizo populations located in the south and the west of the country, respectively, and to compare these frequencies with those of other populations...
July 19, 2017: Human Immunology
https://www.readbyqxmd.com/read/28732776/rad-gtpase-is-essential-for-the-regulation-of-bone-density-and-bone-marrow-adipose-tissue-in-mice
#16
Catherine N Withers, Drew M Brown, Innocent Byiringiro, Matthew R Allen, Keith W Condon, Jonathan Satin, Douglas A Andres
The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca(2+) channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad...
July 18, 2017: Bone
https://www.readbyqxmd.com/read/28732438/investigation-of-killer-immunoglobulin-like-receptor-kir-and-hla-genotypes-to-predict-the-occurrence-of-acute-allograft-rejection-after-kidney-transplantation
#17
Davood Jafari, Mohsen Nafar, Mir Saeed Yekaninejad, Razieh Abdolvahabi, Mahboob Lesan Pezeshki, Efat Razaghi, Ali Akbar Amirzargar
After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR)...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#18
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
2017: PloS One
https://www.readbyqxmd.com/read/28716449/venom-derived-peptides-inhibiting-kir-channels-past-present-and-future
#19
REVIEW
Craig A Doupnik
Inwardly rectifying K+ (Kir) channels play a significant role in vertebrate and invertebrate biology by regulating the movement of K+ ions involved in membrane transport and excitability. Yet unlike other ion channels including their ancestral K + -selective homologs, there are very few venom toxins known to target and inhibit Kir channels with the potency and selectivity found for the Ca2+-activated and voltage-gated K+ channel families. It is unclear whether this is simply due to a lack of discovery, or instead a consequence of the evolutionary processes that drive the development of venom components towards their targets based on a collective efficacy to 1) elicit pain for defensive purposes, 2) promote paralysis for prey capture, or 3) facilitate delivery of venom components into the circulation...
July 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28708886/kir3dl01-upregulation-on-gut-natural-killer-cells-in-response-to-siv-infection-of-kir-and-mhc-class-i-defined-rhesus-macaques
#20
Moritz Ries, Matthew R Reynolds, Ksenia Bashkueva, Kristin Crosno, Saverio Capuano, Trent M Prall, Roger Wiseman, David H O'Connor, Eva G Rakasz, Hajime Uno, Jeffrey D Lifson, David T Evans
Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues...
July 2017: PLoS Pathogens
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