Search results for "Human leukocyte antigen"
showing 10 items of 248 documents
Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci
2011
Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 x 10(-16) and P = 4.1 x 10(-8), respectively).
Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
2010
To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 × 10-29 and rs7755224, combined P = 2.00 × 10-19; r2 = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 × 10-9). © 2010 Nature America, Inc. All rights reserved.
Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells
2018
HLA-E presented antigens are interesting targets for vaccination given HLA-Esâ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector TÂ cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+TÂ cells in the circulation of patients with active tubercu…
Both mature KIR+ and immature KIR- NK cells control pediatric acute B-cell precursor leukemia in NOD.Cg-Prkdcscid IL2rgtmWjl/Sz mice.
2014
Therapeutic natural killer (NK)-cell-mediated alloreactivity toward acute myeloid leukemia has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B-cell precursor leukemia (BCP-ALL) appears to be resistant to NK-cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. In this study, we demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity toward pediatric BCP-ALL in vivo. Notably, both adoptively transferred mature KIR(+)…
Biochemical markers in Celiac disease.
2009
Celiac Disease is a worldwide spread condition affecting 1:100-1:200 individuals. It is a permanent food intolerance to ingested gluten in genetically predisposed subjects. In this review we analyze the biochemical markers of the disease going from laboratory findings to histology passing through genetics. Gluten intolerance is a unique model of autoimmune disease in which we can recognize the main environmental factor (gluten) and the more complex genetic background. In additional way, serological markers for monitoring the disease and a safe and effective therapy (gluten free diet) are also available. In deed the environmental factor such as gluten intake is necessary to trigger the disea…
Identifying SARS‐CoV‐2 ‘memory’ NK cells from COVID‐19 convalescent donors for adoptive cell therapy
2021
Abstract COVID‐19 disease is the manifestation of syndrome coronavirus 2 (SARS‐CoV‐2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus‐infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID‐19 and the main characteristic of SARS‐CoV‐2‐specific‐like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS‐CoV‐2 convalescent donors indicates the presence of ‘memory’/activated NK cells as it ha…
Rapid Expansion of Acute Myeloid Leukemia-Reactive Cytotoxic T Cells from CD8+CD62L+ Blood Lymphocytes of HLA-Matched Healthy Donors In Vitro
2006
Abstract Allogeneic cytotoxic T-lymphocyte (CTL) therapy in acute myeloid leukemia (AML) is hampered by the poor efficiency of growing leukemia-reactive CTLs from healthy donors in vitro. We established an allogeneic mini-mixed lymphocyte-leukemia culture (MLLC) approach by stimulating comparably small numbers (104/well) of CD8+ T cells isolated from healthy donors against irradiated primary AML blasts in 96-well plates. Prior to use, CD8+ T cells were immunomagnetically separated into a CD62L(high)+ subset enriched for naive precursors and central memory cells as well as a CD62L(low)+/negative subset containing effector memory cells. The culture medium contained IL-7, IL-12, and IL-15. Aft…
Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
2014
Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10 -20) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10 -11) near ETS1; 3q28 (rs6444305, p = 1.10 × 10 -10) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10 -10) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10 -8) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRß1 multiallelic amino acids at p…
A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells.
2006
Abstract The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I–restricted immunogenic peptides. One of the tested peptides (YVDFREYEYY) induced in vitro autologous T-cell responses restricted by HLA-A*0101 that were also detectable ex vivo. These peptide-reactive T cells recognized targets transfected with the patient's FLT3-ITD, but not wild-type FLT3, and recognized the patient's AML cells. Our results …
HLA antigens in Sicilian patients affected by chronic myelogenous leukaemia.
1987
SUMMARY HLA antigens were investigated in Sicilian patients with chronic myelogenous leukaemia (CML) and in Sicilian healthy controls. The frequency of the HLA-DRw6 antigen was significantly decreased in the group of patients. These results suggest that DRw6 may be a marker for decreased susceptibility to the etiological or pathogenic mechanism(s) which produce CMLs.