Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Background/Purpose: MicroRNAs are fine tuners of biological pathways that function via post-transcriptional regulation of target mRNA life span. MicroRNA 155 (miR155) is particularly implicated in Rheumatoid Arthritis (RA) pathology through regulation of synovial macrophage cytokine and chemokine production. Thus far miR155 expression across disease activity status has not been examined – to this end we have developed a novel assay of absolute copy number to facilitate such investigation.
Methods: Peripheral blood (PB) was obtained from healthy controls and RA patients who met the 2010 ACR/EULAR diagnostic criteria. CD14+ cells (monocytes) were isolated using micro-beads. The absolute copy numbers of miR-155 transcripts and housekeeping short RNA (U1) in peripheral blood (PB) and synovial fluid (SF) macrophages of RA and healthy controls were assessed using a novel qPCR methodology.
Results: RA PB (n=24) and SF CD14+ monocytes (n=11) expressed higher copy numbers of miR-155 compared with healthy controls (n=22). As expected, RA SF macrophages exhibited the highest expression levels of miR-155 (75318.2/106 copies of RNU1A). In PB monocytes, miR-155 levels were higher when derived from patients with high or moderate disease activity (according to DAS28; p<0.05) than those in remission or healthy controls. The copy number of miR-155 expression was significantly increased in anti-citrullinated protein antibody (ACPA) positive RA (n=17) compared with ACPA negative RA (n=7). The RA PB monocyte miR-155 copy number correlated positively and significantly with DAS28 as a continual variable. There was no correlation between observed increase in miR-155 copy number and patients’ age, disease duration or medication.
Conclusion: Our data demonstrate that miR-155 levels may reflect RA disease activity and could be a potential clinical disease activity biomarker for RA. Moreover our data suggest that circulating monocytes in RA patients exhibit an early activation signature, which is primed for subsequent cytokine release.
D. G. Gilchrist,
I. B. McInnes,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mir-155-expression-correlates-with-clinical-disease-activity-and-has-effector-function-in-rheumatoid-arthritis/