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ORIGINAL PAPER
Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study
Submission date: 2018-01-08
Final revision date: 2018-02-14
Acceptance date: 2018-02-21
Online publication date: 2018-02-28
Publication date: 2018-02-28
Reumatologia 2018;56(1):10-16
KEYWORDS
TOPICS
ABSTRACT
Objectives:
Enhanced/disturbed activities of monocytes are crucial for perpetuation and for development of rheumatoid arthritis (RA). Therefore, knowledge about monocyte activities and regulation of molecular pathways operating within monocytes early in the course of RA development may help to predict the progression to the full-blown disease. We aimed to investigate the profile of miRNAs expression in circulating monocytes and monocyte-related cytokines in sera of individuals at undifferentiated arthritis (UA) stage, wich could serve as new biomarkers for RA development.
Material and methods:
Magnetically sorted monocytes from peripheral blood of 20 UA patients served for total RNA isolation. RNA samples were used for microRNA profiling. Concentrations of CCL3/MIP-1α, M-CSF, CCL2/MCP-1, IL-6, TNF-α and IL-15 in sera of UA patients were measured using ELISA assays. Verification of diagnosis after 4 years of follow-up led to the identification of patients who developed RA (UA -> RA patients) and patients who remained still in UA phase (UA -> UA patients). Comparisons between patients groups were performed using two-tailed Mann-Whitney U test.
Results:
We identified 50 miRNAs in monocytes with the largest variation of expression across all patients samples. From these selected miRNAs, expression of miR-642b-5p, miR-483-3p, miR-371b-5p were significantly up-regulated and miR-25-3p and miR-378d were significantly down-regulated in UA -> RA vs. UA -> UA patients. This specific pattern of miRNAs expression in circulating monocytes paralleled elevated IL-15 and M-CSF concentrations in sera of UA patients who progressed to RA.
Conclusions:
Results of our pilot study indicate that altered activity of monocytes can be detected at early stages of RA. We found new miRNA candidates differentially expressed in peripheral blood monocytes and elevated concentrations of IL-15 and M-CSF involved in monocyte activity and differentiation in patients with UA who subsequently developed RA, in comparison to UA patients who did not progress to RA after 4 years follow-up.
Enhanced/disturbed activities of monocytes are crucial for perpetuation and for development of rheumatoid arthritis (RA). Therefore, knowledge about monocyte activities and regulation of molecular pathways operating within monocytes early in the course of RA development may help to predict the progression to the full-blown disease. We aimed to investigate the profile of miRNAs expression in circulating monocytes and monocyte-related cytokines in sera of individuals at undifferentiated arthritis (UA) stage, wich could serve as new biomarkers for RA development.
Material and methods:
Magnetically sorted monocytes from peripheral blood of 20 UA patients served for total RNA isolation. RNA samples were used for microRNA profiling. Concentrations of CCL3/MIP-1α, M-CSF, CCL2/MCP-1, IL-6, TNF-α and IL-15 in sera of UA patients were measured using ELISA assays. Verification of diagnosis after 4 years of follow-up led to the identification of patients who developed RA (UA -> RA patients) and patients who remained still in UA phase (UA -> UA patients). Comparisons between patients groups were performed using two-tailed Mann-Whitney U test.
Results:
We identified 50 miRNAs in monocytes with the largest variation of expression across all patients samples. From these selected miRNAs, expression of miR-642b-5p, miR-483-3p, miR-371b-5p were significantly up-regulated and miR-25-3p and miR-378d were significantly down-regulated in UA -> RA vs. UA -> UA patients. This specific pattern of miRNAs expression in circulating monocytes paralleled elevated IL-15 and M-CSF concentrations in sera of UA patients who progressed to RA.
Conclusions:
Results of our pilot study indicate that altered activity of monocytes can be detected at early stages of RA. We found new miRNA candidates differentially expressed in peripheral blood monocytes and elevated concentrations of IL-15 and M-CSF involved in monocyte activity and differentiation in patients with UA who subsequently developed RA, in comparison to UA patients who did not progress to RA after 4 years follow-up.
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Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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