Bringing new players into the field : onco-pharmacovigilance in the era of cardio-oncology

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Frequent loss of heterozygosity without loss of genetic material in acute myeloid leukemia with a normal karyotype

We performed a whole-genome loss of heterozygosity (LOH) analysis of 32 cases of acute myeloid leukemia with normal karyotype using high-density single nucleotide polymorphism arrays. LOH was found in 20% of cases. We identified two types of LOH: (i) interstitial, characterized by small deletions of genomic DNA (2-8 Mb), and (ii) terminal, involving large (30-90 Mb) telomeric regions. Surprisingly, terminal LOH occurred without loss of genetic material because of deletion of large chromosome regions and their substitution through the duplication of the corresponding regions from the homologous chromosomes (acquired partial uniparental disomy). (copyright) 2005 Wiley-Liss, Inc

Helicobacter pylori, asthma and allergy

Bronchial asthma and allergic diseases are orchestrated by T-cells producing T-helper type 2 (Th2) cytokines, such as interleukin-4 (IL-4) and IL-5, and are inhibited by Th1 responses. Helicobacter pylori has chronically infected the human population for c. 100 000 years and preferentially elicits a Th1 mucosal immune response with the production of interferon-\u3b3 and IL-12. Among several bacterial factors, the neutrophil-activating protein of H. pylori (HP-NAP) not only plays a key role in driving Th1 inflammation but it is also able to inhibit Th2 responses in vitro and in vivo in allergic bronchial asthma, in humans and mice. Both systemic and mucosal administrations of HP-NAP are successful in reducing eosinophilia, immunoglobulin E and systemic Th2 cytokines at the bronchial level. Thus, these results identify HP-NAP as a candidate for novel strategies for the prevention and treatment of allergic diseases

HP0175 Promotes the Production of IL-23, IL-6, IL-1β and TGF-β

Helicobacter pylori infection induces a chronic gastric inflammatory infiltrate. This study was undertaken to evaluate the type of the innate immune responses elicited by the secreted peptidyl-prolyl cis-trans isomerase of H. pylori (HP0175). The cytokine production induced by HP0175 in neutrophils, and monocytes was evaluated. HP0175 was able to induce the expression of IL-23 in neutrophils, and monocytes, and IL-6, IL-1beta and TGF-beta in monocytes. These findings indicate that HP0175 is able to promote the activation of innate cells and the production of a cytokine milieu that may favour the development of Th17 response

Interferon γ-Signature Transcript Profiling and IL-23 Upregulation in Response to Helicobacter Pylori Infection

International audienceHelicobacter pylori infection is the major cause of gastroduodenal pathologies including gastric cancer. The long persistence of bacteria and the type of immune and inflammatory response determine the clinical issue. In this study, the global gene expression profile after 6 and 12 months of H. pylori infection was investigated in the mouse stomach, using the Affymetrix GeneChip Mouse Expression Array A430. Genes related to the inflammatory and immune responses were focused. Levels of selected transcripts were confirmed by reverse transcription polymerase chain reaction. Twenty-five and nineteen percent of the differentially expressed genes observed at 6 and 12 months post-infection respectively, were related to immune response. They are characterized by an interferon (IFN)γ-dependent expression associated to a T helper 1 (Th1) polarised response. In-depth analysis revealed that an up-regulation of IL-23p19, took place in the stomach of H. pylori infected-mice. Strong IL-23p19 levels were also confirmed in gastric biopsies from H. pylori-infected patients with chronic gastritis, as compared to healthy subjects. Our microarray analysis revealed also, a high decrease of H + K + -ATPase transcripts in the presence of the H. pylori infection. Association of gastric Th1 immune response with hypochlorhydria through the down-regulation of H + K + -ATPase contributes to the genesis of lesions upon the H. pylori infection. Our data highlight that the up-regulation of IL-23 and of many IFNγ signature transcripts occur early on during the host response to H. pylori, and suggest that this type of immune response may promote the severity of the induced gastric lesions

LIOFeron®TB/LTBI: A novel and reliable test for LTBI and tuberculosis

© 2019 The Author(s) Objectives: High accuracy diagnostic screening tests for tuberculosis (TB) are required to improve the diagnosis of both active TB and latent Mycobacterium tuberculosis (MTB) infection (LTBI). The novel IGRA LIOFeron®TB/LTBI assay was tested and its accuracy was compared to the QuantiFERON®-TB Gold Plus assay. Methods: A total of 389 subjects were enrolled in two cohorts and classified as healthy, active TB or LTBI persons. The blood of all the patients was tested with LIOFeron®TB/LTBI assay, containing MTB alanine dehydrogenase, able to differentiate active TB from LTBI diagnosis. The results obtained with both IGRAs, performed on the same 250 samples, were finally compared. Results: The two assays demonstrated an excellent concordance of their results with patients’ diagnosis of MTB infection. ROC analysis for QuantiFERON®-TB Gold Plus showed sensitivity and specificity respectively of 98% and 97% in diagnosing active TB patients and 85% and 94% in diagnosing LTBI subjects. LIOFeron®TB/LTBI assay showed sensitivity and specificity respectively of 90% and 98% in diagnosing active TB patients and 94% and 97% in diagnosing LTBI subjects. Conclusions: The two IGRAs displayed the same high accuracy in diagnosing MTB infection/TB disease, and LIOFeron®TB/LTBI assay demonstrated higher sensitivity than QuantiFERON®-TB Gold Plus test in LTBI detection

Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity

Human autoimmune gastritis (AIG) is a chronic inflammatory disorder of the gastric corpus. We have defined the antigen repertoire and the functional properties of in vivo activated CD4+ T cells derived from the gastric mucosa of patients with AIG. A remarkable proportion of the CD4+ T cell clones proliferated in response to H+,K+-ATPase. Six epitopes identified in the alpha chain, and 5 in the beta chain, of gastric K+,K+-ATPase were recognized by autoreactive gastric T cell clones. The majority of the autoreactive T cell clones secreted IFN-gamma and showed a T helper 1 (Th1) profile. All clones produced TNF-alpha,provided help for B cell immunoglobulin production, expressed perforin-mediated cytotoxicity, and most induced Fas-Fas ligand-mediated apoptosis. Data suggest that activation of gastric H+,K+-ATPase-specific Th1 T cells is crucial in the pathogenesis of human gastric autoimmunity and atroph