Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Parameters/ predictors of treatment response in patients with early rheumatoid arthritis (ERA) are needed to optimize treatment management based on the expected disease course. miRNAs are stable in cell-free form in body fluids and have therefore a potential to serve as biomarkers for diagnosis and treatment response. Our aim was to analyze the association between the expression of miRNAs in sera of patients with ERA with disease activity and outcome.
Methods:
The study included 34 patients with ERA (64.52% RF+, 51.61% ACPA+) who fulfilled 2010 ACR/EULAR classification criteria for RA with symptom duration <8 months. Total RNA was isolated using phenol-chloroform extraction from whole sera obtained at baseline and after 3 months of therapy with DMARDs. The expression of miR-146a, 155, 223, 203, 132, 124a, 16 and let-7a was analyzed using specific primers by TaqMan Real-Time PCR. Peripheral blood mononuclear cells (PBMC) were treated with methotrexate (MTX, 25ug/ml) in vitro.
Results:
In treatment naïve ERA patients, the expression of miR-223 positively correlated with baseline DAS28 (p=0.031), with change of DAS28 (DDAS28) calculated as the difference between DAS28 at 3 months follow up and baseline (p=0.014), CRP (p=0.008) and peripheral leukocyte count (p=0.007). After treatment, the correlation of miR-223 with the leukocyte count remained significant (p=0.004). Levels of miR-223 were lower in patients with positivity of both RF and ACPA in comparison with patients that were RF+/ACPA-, RF-/ACPA+ or RF-/ACPA- (p=0.02). None of the other miRNAs analysed in our study were associated with clinical activity of ERA.
Expression of miR-223 was significantly decreased after 3 months of treatment with DMARDs in comparison with baseline (p=0.007). Further analysis revealed 2 groups of patients with opposing change in the expression of miR-223. One group (“miR-223/-“, n=24; 52.4% RF+, 30.1% ACPA+) developed decreased levels of miR-223 (p<0.0001) while another group (“miR-223/+”, n=10; 90% RF+, 80% ACPA+) showed an increase in miR-223 expression after treatment (p=0.002). In the miR-223/- group, the baseline levels of miR-223 correlated with DDAS28 (p=0.039) and the change in miR-223 was associated with DDAS28 (p=0.007). In contrast, no correlations between miR-223 and parameters of disease activity were found in the miR-223/+ group.
The change in expression of miR-223 in sera may be attributable to the change in number of leukocytes between 3 months and baseline concluded from the positive correlations between these variables (p=0.025). In addition, the expression of miR-223 in PBMC is downregulated by 15% (p=0.001) after treatment with MTX.
Conclusion: Our data support the potential of miR-223, known to be upregulated in T cells in RA (Sebastini GD et al. 2011), to serve as a marker of disease activity in patients with treatment naïve ERA and its association with disease outcome in a short time follow up. We hypothesize that differential expression of miR-223 in RF+/ACPA+ patients may characterize ERA patients who are at risk of more severe disease progression.
Acknowledgement: This work was supported by IMI BTCure, IAR, Masterswitch-PF7, Articulum, OPPA and MH CR project No.023728.
Disclosure:
M. Filkova,
none,
2;
C. Ospelt,
none,
3;
S. Vettori,
none,
3;
L. ŠEnolt,
none,
2;
H. F. Mann,
none,
2;
B. A. Michel,
none,
3;
J. Vencovsky,
none,
2;
K. Pavelka,
none,
3;
R. E. Gay,
none,
2;
S. Gay,
None,
2;
A. Jüngel,
none,
2.
« Back to ACR/ARHP Annual Meeting 2012
ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-mir-223-is-associated-with-disease-activity-and-may-predict-the-response-to-therapy-in-treatment-naive-patients-with-early-rheumatoid-arthritis/