Dataset Information

A "crossomics" study analysing variability of different components in peripheral blood of healthy caucasoid individuals.

ABSTRACT:

Background

Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable.

Methodology/principal findings

To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics" analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4+T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset.

Conclusions/significance

Our study shows that the intra-individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective.

SUBMITTER: Gruden K

PROVIDER: S-EPMC3257221 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

A "crossomics" study analysing variability of different components in peripheral blood of healthy caucasoid individuals.

Gruden Kristina K Hren Matjaž M Herman Ana A Blejec Andrej A Albrecht Tanja T Selbig Joachim J Bauer Chris C Schuchardt Johannes J Or-Guil Michal M Zupančič Klemen K Svajger Urban U Stabuc Borut B Ihan Alojz A Kopitar Andreja Nataša AN Ravnikar Maja M Knežević Miomir M Rožman Primož P Jeras Matjaž M

PloS one 20120112 1

<h4>Background</h4>Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable.<h4>Methodology/principal findings</h4>To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers wa ...[more]

PMID: 22253695

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Project description:Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCGRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including HIV infection. To gain insight into the developmental relationship and functions of CD16+ and CD16- Mo, we examined transcriptional profiles of these Mo subsets in peripheral blood from healthy individuals. Of 16,328 expressed genes, 2,759 genes were differentially expressed and 228 and 250 were >2-fold upregulated and downregulated, respectively, in CD16+ compared to CD16- Mo. CD16+ Mo were distinguished by upregulation of dendritic cell (DC) (SIGLEC10, CD43, RARA) and macrophage (MF) (CSF1R/CD115, MafB, CD97, C3aR) markers together with transcripts relevant for DC-T cell interaction (CXCL16, ICAM-2, LFA-1), cell activation (LTB, TNFRSF8, LST1, IFITM1-3, HMOX1, SOD-1, WARS, MGLL), and negative regulation of the cell cycle (CDKN1C, MTSS1), whereas CD16- Mo were distinguished by upregulation of myeloid (CD14, MNDA, TREM1, CD1d, C1qR/CD93) and granulocyte markers (FPR1, GCSFR/CD114, S100A8-9/12). Differential gene expression in CD16+ and CD16- Mo was confirmed by quantitative real time RT-PCR (i.e., CD16, C3AR1, C1QR1, ICAM-2, CSF1R, CSF3R, CDKN1C, TNFRSF1, and LTB) and flow cytometry (i.e., CSF1R, CSF3R, C1QR1, C3AR1, CD1d, CD43, CXCL16, and CX3CR1). Furthermore, increased expression of RARA and KLF2 transcripts in CD16+ Mo coincided with absence of cutaneous lymphocyte associated antigen (CLA) expression, indicating potential imprinting for non-skin homing. These results suggest that CD16+ and CD16- Mo originate from a common myeloid precursor, with CD16+ Mo having a more MF- and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16+ and CD16- Mo give rise to functionally distinct DC and MF in vivo.

Dataset Information

A "crossomics" study analysing variability of different components in peripheral blood of healthy caucasoid individuals.

Background

Methodology/principal findings

Conclusions/significance

Publications

A "crossomics" study analysing variability of different components in peripheral blood of healthy caucasoid individuals.

Similar Datasets

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