Project description:Human cytomegalovirus (HCMV) reactivation is a leading infectious cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HCMV reactivation is characterized by detection of viral DNA in the blood (DNAemia), however, the role of the blood compartment during HCMV reactivation is not well characterized. Using powerful molecular tools, we characterized HCMV infection in Peripheral Blood Mononuclear Cells (PBMCs) during DNAemia in HCMV reactivating HSCT patients. Surprisingly we found that all PBMC populations harbored extremely low levels of viral DNA and extremely low levels of viral transcripts. Remarkably, the viral transcripts detected in these samples were mainly immediate early genes indicating that these cells do not go through a full productive cycle. Analysis of the cellular transcriptome revealed characteristic transcriptional changes in high DNAemic samples implying the development of HCMV-specific T cells and inhibition of regulatory T cell function. Overall, our data indicate that DNAemia in HCMV reactivating HSCT patients is associated with distinct immune signatures but is not necessarily accompanied by substantial infection of PBMCs, and that PBMCs are not productively infected. These findings are important for understanding the role of the blood compartment in progression and control of HCMV during reactivation.
Project description:Here we present genome-wide genotyping data of 70 human samples from Europe (Balto-Slavic speakers, Greeks) that are used in addition to public data in a study of genetic heritage of the Balto-Slavic populations.
Project description:AIM: To investigate the adaptive properties of NK cells, by comparing the expression profiles of FACS-sorted KIR+ (CD158b1b2j) and KIR- NK cells from patients experiencing or not a Cytomegalovirus (HCMV) reactivation after haploidentical hematopoietic stem cell transplantation (h-HSCT). RESULTS: Our flow cytometry data demonstrate that KIR+ NK cells are expanded in h-HSCT patients upon HCMV reactivation, thus suggesting that these cells could be important in controlling the viral infection and could be endowed with adaptive features. By comparing the expression profiles of KIR+ and KIR- NK cells from reacivated patients, we demonstrated a cytokine receptor unbalance, a prevalence of pathways associated to mitochondrial respiration and consequent ATP synthesis, a downregulation of genes involved in epigenetic reprogramming, all properties attributable adaptive NK cells. By comparing the molecular fingerprint of KIR+ NK cells between patients experiencing a HCMV reactivation and not reactivated patients, we observed in reactivated group an upregulation of INFG expression and in genes involved in Signaling receptor activity and MHC class II antigen presentation , thus strengthens the hypothesis that our KIR+ NK cells in reactevated h-HSCT patients are able to produce IFN-γ driving specific responses upon re-stimulation. However, the enrichment in PD-1 signaling, let us speculate that KIR+ NK cells from reactivated h-HSCT patients have impaired effector-functions.
Project description:Reconstitution of cell lines and occurrence of complications following hematopoietic stem cell transplantation (HSCT) are regulated by genome expression. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare whole genome expression in children before and after HSCT. A total of 44 children treated with HSCT were enrolled in the study. Gene expression was measured before HSCT (pre-HSCT group; n=44) and after a median of 6 months after allogenic HSCT (post-HSCT group; n=27; all children were included in the pre-HSCT group). Neoplasms were the indication for HSCT in 73% of the patients. Whole genome expression was assessed in leukocytes using GeneChip® HumanGene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed 18 significantly different genes with defined function. These genes are responsible for proliferation and differentiation of cells (14 genes), apoptosis (8 genes), migration of cells (3 genes) and fluid/electrolyte homeostasis (2 genes). Our findings allow us to conclude that activation of genes involved in reconstitution of donor cell lines, and those related to immune reactions observed after HSCT, form the genetic background for physiological and pathological processes following HSCT.
Project description:To study the population genetics context of the Saqqaq individual we carried out Illumina Bead-Array-based genotyping on four native North American and twelve north Asian populations.
Project description:Differencies between groups between pre and post haematopoietic stem cell transplantation children Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT) in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip® HumanGene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT.