Association of SARS-CoV-2 immunoserology and vaccination status with myocardial infarction severity and outcome.

Background: The COVID-19 pandemic adversely affected the severity and prognosis of patients with acute myocardial infarction (MI) caused by atherothrombosis (type 1 MI). The effect, if any, of COVID-19 vaccination and natural SARS-CoV2 serologic immunity in these patients is unclear. Our aim was to analyze the association between the severity and outcome of patients with type 1 MI and their previous SARS-CoV2 vaccination and serostatus.

Donor Lung Preservation at 10°C: Clinical and Logistical Impact.

Introduction: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics.

Methods: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns.

SARS-COV-2 seroprevalence among all healthcare workers in a tertiary hospital in Spain.

Background: Healthcare workers (HCWs) have been a critical and vulnerable population during SARS-CoV-2 pandemic. The aim of this study was to determine the overall seroprevalence and to evaluate occupational risk factors among HCWs in one of the countries most affected by this pandemic.

Methods: We conducted a seroprevalence study for SARS-CoV-2 in a tertiary hospital in Madrid (Spain) between 24 April and 8 May 2020.

Biallelic ATM alterations detected at diagnosis identify a subset of treatment-naïve chronic lymphocytic leukemia patients with reduced overall survival similar to patients with p53 deletion.

The prognostic impact of biallelic ATM abnormalities (ATM mutation and concurrent 11q deletion) remains unknown. We studied ATM, BIRC3, SF3B1, and NOTCH1 genes in 118 treatment-naïve CLL patients at diagnosis. Patients with biallelic ATM alteration had a similar time to first treatment (TTFT) and shorter overall survival (OS) compared with patients with isolated 11q deletion and shorter TTFT and OS when compared to patients with wild-type ATM.

Association of DDX58 177 C > T polymorphism with decreased risk of Epstein-Barr virus-related nodular sclerosis classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is frequently related to Epstein-Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV-host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response.

HLA Allele E*01:01 Is Associated with a Reduced Risk of EBV-Related Classical Hodgkin Lymphoma Independently of HLA-A*01/*02.

Background: An inefficient immune response against Epstein-Barr virus (EBV) infection is related to the pathogenesis of a subgroup of classical Hodgkin lymphomas (cHL). Some EBV immune-evasion mechanisms target HLA presentation, including the non-classical HLA-E molecule. HLA-E can be recognized by T cells via the TCR, and it also regulates natural killer (NK) cell signaling through the inhibitory CD94/NKG2A receptor.

Vascular endothelial growth factor A (VEGFA) gene polymorphisms have an impact on survival in a subgroup of indolent patients with chronic lymphocytic leukemia.

Vascular endothelial growth factor (VEGF)-mediated angiogenesis contributes to the pathogenesis of B-cell chronic lymphocytic leukaemia (CLL). We investigated the impact of VEGFA gene diversity on the clinical outcome of patients with this disease. A VEGFA haplotype conformed by positions rs699947 (-1540C>A), rs833061 (-460T>C) and rs2010963 (405C>G) and two additional single-nucleotide polymorphisms (SNPs), rs3025039 (936C>T) and rs25648 (1032C>T), were analysed in 239 patients at the time of their CLL diagnosis.

KIR2DL5: An Orphan Inhibitory Receptor Displaying Complex Patterns of Polymorphism and Expression.

A recently developed anti-KIR2DL5 (CD158f) antibody has demonstrated KIR2DL5 expression on the surface of NK and T lymphocytes, making it the last functional KIR identified in the human genome. KIR2DL5 belongs to an ancestral lineage of KIR with Ig-like domains of the D0-D2 type, of which KIR2DL4, an HLA-G receptor, is the only other human member. Despite KIR2DL4 and KIR2DL5 being encoded by genes with similar domain usage, several KIR2DL5 functions resemble more closely those of KIR recognizing classical HLA class I molecules - surface-expressed KIR2DL5 inhibits NK cells through the SHP-2 phosphatase and displays a clonal distribution on NK and T lymphocytes.

New mutations in chronic lymphocytic leukemia identified by target enrichment and deep sequencing.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified.

KIR typing by non-sequencing methods: polymerase-chain reaction with sequence-specific primers.

The killer-cell immunoglobulin-like receptors (KIR), which enable NK cells to detect allogeneic target cells and abnormalities in the expression of self-HLA molecules, are encoded by genes that display extensive copy number variation. These variations in the KIR genotype are relevant for multiple aspects of human health, including therapy of cancer. PCR with sequence-specific primers (SSP) is simplest and most widely used among techniques for studying KIR genotypes.

Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity.

HSV-1 establishes life-long latency that can result in clinical relapses or in asymptomatic virus shedding. Although virtually all adults have been exposed to HSV-1, the clinical course varies remarkably. Genetic host variability could be related to this clinical diversity.

Molecular characterisation of KIR2DS2*005, a fusion gene associated with a shortened KIR haplotype.

KIR2DS2 is an activating homologue of KIR2DL2, an inhibitory killer-cell immunoglobulin-like receptor (KIR) that surveys expression of major histocompatibility complex-C allotypes bearing a C1 epitope. We have studied here its allele KIR2DS2*005, which shows a hybrid structure-it is identical to other KIR2DS2 alleles in the ectodomain, but has transmembrane and cytoplasmic regions identical to those of KIR2DS3(*)001, a short-tailed KIR of uncertain expression and function. Our results reveal that KIR2DS2*005 is a fusion gene-the product of an unequal crossing over by which the genes KIR2DS2 and KIR2DS3 recombined within a 400 base pair region of complete identity in intron 6.

The cannabinoid receptor 1 gene (CNR1) and multiple sclerosis: an association study in two case-control groups from Spain.

Different studies point to the implication of the endocannabinoid system in multiple sclerosis (MS) and animal models of MS. The purpose of this study was to evaluate a possible association of MS with polymorphic markers at the CNR1 gene, encoding the cannabinoid 1 (CB(1)) receptor. We have performed a genetic analysis of an AAT repeat microsatellite localized in the downstream region of the CNR1 gene, in two case-control groups of MS patients and healthy controls (HC) from Spain (Madrid and Bilbao).

The 5' intergenic, promoter, pseudoexon 3 and complete coding sequences of the hybrid gene KIR2DS3*002.

Genomic and mRNA sequences support the KIR2DS3*002 gene being a hybrid of KIR2DS3*00103 and KIR2DS5.

Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes.

The KIR2DS3 gene is an activating homologue of the inhibitory killer-cell immunoglobulin-like receptors (KIR) that recognize HLA-C molecules, enabling NK cells to survey the normal function of endogenous antigen presentation. The genetics of KIR2DS3 is complicated by the existence of alleles with similar coding sequences that map to different regions of the KIR complex in chromosome 19, or whose location in this complex is unknown. Here, by studying the family segregation of the KIR alleles 2DS3*001, *002 and *003N, and the distribution of these in unrelated individuals, we demonstrate the existence of two paralogous KIR2DS3 genes that can be inherited separately or, as it happens frequently in Caucasoids due to linkage disequilibrium, together.

Facilitation of KIR genotyping by a PCR-SSP method that amplifies short DNA fragments.

Detection of killer-cell immunoglobulin-like receptors (KIR) genes by polymerase chain reaction with sequence-specific primers (PCR-SSP) led in 1997 to the discovery that human genomes diverge largely in the KIR they encode. While only a few KIR genes are conserved in all humans, most individuals lack several those genes, which tend to associate in diverse haplotypic combinations. The PCR-SSP technique, updated to detect the more recently identified KIR genes and alleles, is still used widely to analyze the diversity of human populations, and to study the influence of KIR-gene variability on human health.

An apparent KIR2DS2-negative KIR2DL2-positive genotype discloses the novel allele KIR2DS2*00104.

KIR2DS2*00104 lacks a distinctive synonymous substitution of KIR2DS2 in nucleotide 418 that affects KIR genotyping.

Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2.

Herpes simplex virus type 1 (HSV-1) causes lifelong latent infections in most humans. Periodical virus reactivations from latency in the neurons of sensitive ganglia lead to transport to mucocutaneous regions and productive replication, which results in recurrent inflammatory herpetic lesions or in asymptomatic virus shedding. The medical consequences of such lesions and the frequency of recurrences vary greatly in different subjects.

Human KIR2DL5 is an inhibitory receptor expressed on the surface of NK and T lymphocyte subsets.

Human NK cells, by means of a repertoire of clonally distributed killer cell Ig-like receptors (KIR), survey the expression of individual self HLA class I molecules, which is often altered in infections and tumors. KIR2DL5 (CD158f) is the last identified KIR gene and, with KIR2DL4, constitutes a structurally divergent lineage conserved in different primate species. Research on KIR2DL5 has thus far been limited to its genetic aspects due to a lack of reagents to detect its product.

Complete coding sequences and haplotypic associations of HLA-B*0707, -B*1524, -B*4405, -B*4802, -DRB1*0409, -DRB1*0411, -DRB1*1115, -DRB1*1305, and the novel allele -DRB1*0709. Group-specific amplification of cDNA from DRB1 alleles associated to DRB3 and DRB4.

We present here the characterization of the complete coding sequences, previously unavailable, of the human leukocyte antigen (HLA) alleles B*0707, B*1524, B*4405, B*4802, DRB1*0409, DRB1*0411, DRB1*1115, DRB1*1305, and that of a new allele, DRB1*0709. For the isolation of cDNA from the DRB1 gene, we designed a novel set of polymerase chain reaction (PCR) primers that makes it possible to amplify separately the groups of DRB1 alleles associated to each of the DRB3 and DRB4 loci. The primary structures, functional features, evolutionary relationships, haplotypic associations, and population distributions of each of the nine HLA-B and -DRB1 alleles reported here are reviewed.

Three structurally and functionally divergent kinds of promoters regulate expression of clonally distributed killer cell Ig-like receptors (KIR), of KIR2DL4, and of KIR3DL3.

The generation of killer cell Ig-like receptor (KIR) expression patterns in NK cells involves variegated silencing of KIR genes by DNA methylation. To identify regulatory elements involved in KIR gene activation, upstream regions of KIR genes were functionally characterized in NK3.3 cells as well as in primary NK cells.

The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated.

Killer-cell Ig-like receptors (KIR) are structurally and functionally diverse, and enable human NK cells to survey the expression of individual HLA class I molecules, often altered in infections and tumors. Multiple events of non-reciprocal recombination have contributed to the rapid diversification of KIR. We show that approximately 4.