02.30 High levels of mir-451a differentiate patients with clinically suspect arthralgia from healthy controls

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Abstract

Background

Individuals with clinically suspect arthralgia (CSA) with positivity of anti-citrullinated protein antibodies (ACPA) are considered at high risk of developing rheumatoid arthritis (RA). The altered expression of miRNAs is involved in the development and maintenance of autoimmune diseases. We aimed to investigate differentially expressed miRNAs in peripheral blood mononuclear cells (PBMC) in CSA and healthy controls (HC).

Material and methods

The study included 19 CSA and 20 HC. Disease activity assessments and ultrasound of 28 small joints was performed in CSA. Total RNA from PBMC was isolated. A comprehensive analysis of miRNAs was performed using TaqMan Low Density Array (TLDA) in 5 samples per group. Single assay analysis of miR-451a, CXCL16 and IL-8 was performed in remaining samples and normalised to RNU44 or ACTB, respectively. dCt was used for relative quantification.

Results

TLDA analysis revealed 2.43x higher levels of miR-451a in CSA compared to HC. Further validation next confirmed 3.19x higher expression of miR-451a in CSA (p≤0.001).

Results

CXCL16 and IL-8 were predicted as miR-451a targets. Expression of miR-451 positively correlated with CXCL16 (r=0.497; p=0.030) in CSA and IL-8 in both CSA (r=0.485; p=0.035) and HC (r=0.617; p=0.004). This is suggestive of an indirect regulation by miR-451 and a specific role of CXCL16 in CSA. Moreover, the expression of both CXCL16 (1.51x; p=0.013) and IL-8 (3.17x; p=0.032) was higher in CSA compared to HC.

Results

By definition, all CSA individuals had swollen joint count 0. Ten CSA had some degree of subclinical activity on ultrasound (GC>1/PD>0). Levels of miR-451 significantly correlated with DAS28-CRP (r=0.575; p=0.010), SDAI (r=0.676; p=0.004) and VAS (r=0.484; p=0.036). CXCL16 correlated with tender joint count (r=0.576; p=0.010). Subclinical activity as per US had no effect on the levels of miR-451a, CXCL16 or IL-8 in PBMC.

Conclusions

Although CSA cannot be considered a disease itself, and is rather a clinical suspicion of a disease, high levels of miR-451a in PBMC distinguish these individuals at high risk of developing RA. Moreover, miR-451 in PBMC reflects the activity at this pre-clinical phase and correlates with CXCL16 with a role in angiogenesis and chemotaxis.

Acknowledgement

Projects MHCR 023728, SVV 2 60 263.

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