Human peripheral blood mononuclear cells as a valuable source of disease‐related biomarkers: Evidence from comparative proteomics studies

Abstract

PurposeThe discovery of specific and sensitive disease‐associated biomarkers for early diagnostic purposes of many diseases is still highly challenging due to various complex molecular mechanisms triggered, high variability of disease‐related interactions, and an overlap of manifestations among diseases. Human peripheral blood mononuclear cells (PBMCs) contain protein signatures corresponding to essential immunological interplay. Certain diseases stimulate PBMCs and contribute towards modulation of their proteome which can be effectively identified and evaluated via the comparative proteomics approach.Experimental designIn this review, we made a detailed survey of the PBMCS‐derived protein biomarker candidates for a variety of diseases, published in the last 15 years. Articles were preselected to include only comparative proteomics studies.ResultsPBMC‐derived biomarkers were investigated for cancer, glomerular, neurodegenerative/neurodevelopmental, psychiatric, chronic inflammatory, autoimmune, endocrinal, infectious, and other diseases. A detailed review of these studies encompassed the proteomics platforms, proposed candidate biomarkers, their immune cell type specificity, and potential clinical application.ConclusionsOverall, PBMCs have shown a solid potential in giving early diagnostic and prognostic biomarkers for many diseases. The future of PBMC biomarker research should reveal its full potential through well‐designed comparative studies and extensive testing of the most promising protein biomarkers identified so far.

Mass Spectrometric Detection of Formaldehyde-Crosslinked PBMC Proteins in Cell-Free DNA Blood Collection Tubes

“…The value of PBMCs for proteomic studies to investigate disease biomarkers has previously been discussed [7]. Our study demonstrates conclusively that formaldehyde crosslinking occurs between proteins in PBMCs from blood samples collected in Streck tubes.…”

Ex Vivo 13C-Metabolic Flux Analysis of Porcine Circulating Immune Cells Reveals Cell Type-Specific Metabolic Patterns and Sex Differences in the Pentose Phosphate Pathway

“…For the parallel isotopic labeling experiments, 5 × 10 6 purified granulocytes and PBMCs were resuspended in 1 mL RPMI medium (Genaxxon bioscience, Ulm, Germany, detailed composition is listed in the Supplementary Material) spiked with an isotopic tracer (all from Cambridge Isotope Laboratories, Andover, MA, USA) containing [1,2-13 C]glucose, [4,5,[6][7][8][9][10][11][12][13] C]glucose, [U- 13 C]glucose (each labeled/unlabeled, 1:1, w/w) or [U- 13 C]glutamine (100% labeled), respectively (n = 2, for each 13 C-tracer experiment). The incubation was performed in a closed 2 mL tube at 37 • C under constant vertical rotation at 5 rpm (Trayster Digital, IKA, Staufen, Germany) for 2 h. After incubation, the cells were spun down and 850 µL of the supernatant were transferred into a vial and subsequently stored at −20 • C until the GC-MS analysis of the 13 CO 2 enrichment and lactate.…”

“…They comprise monocytes and lymphocytes (T cells, B cells, and natural killer cells) and, therefore, represent cells of both innate and adaptive immunity. Due to their accessibility in circulation and involvement in health and disease, PBMCs have been suggested as potential biomarkers, e.g., in heart failure and septic shock [11][12][13][14][15]. In contrast to granulocytes, which require mainly glycolytic pathways for energy production and antimicrobial defense [16,17], PBMCs have a higher mitochondrial O 2 consumption and primarily utilize glutamine via the TCA cycle for proliferation, differentiation, and the effector function [18].…”