Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiling in CD69 positive blood cells selected from Healthy blood Donors and HTLV-1-infected patients

ABSTRACT: The goal of the study was to identify difference in gene expression between activated /CD69+ blood cells selected from HTLV-1-infected patient displaying HAM-TSP disease (HTLV-1-associated myelopathy/tropical spastic paraparesis), compared to healthy blood donor /HD (biological sample providers: Dr. Antoine Gessain, Pasteur Institute Paris and Etablissement FranM-CM-'ais du Sang) We performed microarray gene expression profiling of Immune cells selected on the marker of early activation, CD69, by the use of MACS beads (Miltenyi Biotec), from 10.106 blood cells of two healthy blood donors and two HAM/TSP patients

ORGANISM(S): Homo sapiens

SUBMITTER: Pascale GIRAUDON

PROVIDER: E-GEOD-33859 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Human T lymphotropic virus type 1 increases T lymphocyte migration by recruiting the cytoskeleton organizer CRMP2.

Varrin-Doyer Michel M Nicolle Adeline A Marignier Romain R Cavagna Sylvie S Benetollo Claire C Wattel Eric E Giraudon Pascale P

Journal of immunology (Baltimore, Md. : 1950) 20120106 3

Recruitment of virus-infected T lymphocytes into the CNS is an essential step in the development of virus-associated neuroinflammatory diseases, notably myelopathy induced by retrovirus human T leukemia virus-1 (HTLV-1). We have recently shown the key role of collapsin response mediator protein 2 (CRMP2), a phosphoprotein involved in cytoskeleton rearrangement, in the control of human lymphocyte migration and in brain targeting in animal models of virus-induced neuroinflammation. Using lymphocyt ...[more]

PMID: 22227566

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Project description:Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as a surrogate CSF biomarker to identify HAM/TSP patients with a worse prognosis.

Dataset Information

Gene expression profiling in CD69 positive blood cells selected from Healthy blood Donors and HTLV-1-infected patients

Publications

Human T lymphotropic virus type 1 increases T lymphocyte migration by recruiting the cytoskeleton organizer CRMP2.

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