ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 522

Whole Blood microRNA Signature for Primary Sjögren’s Syndrome-Related Lymphoma

Jessica Tarn1, Simon Cockell2, Colin Gillespie3, Shereen Al-Ali1,4, Katherine James1, James Locke1, Simon Bowman5, Bridget Griffiths6, David Young1 and Wan-Fai Ng7, 1Newcastle University, Newcastle upon Tyne, United Kingdom, 2Bioinformatics Support Unit, Newcastle University, Newcastle upon Tyne, United Kingdom, 3School of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne, United Kingdom, 4College of Science, University of Basrah, Basrah, Iraq, 5Rheumatology Dept (Selly Oak), University Hospital Birmingham, Birmingham, United Kingdom, 6Rheumatology, Freeman Hospital, Newcastle Upon Tyne, United Kingdom, 7Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Sjogren's Syndrome: Pathophysiology

Session Type: Abstract Submissions (ACR)

Background/Purpose

Micro RNAs (miRNAs) are 18-25nt non-coding RNAs that bind target/complementary sequences within the 3’UTR of RNA molecules steering them towards degradation or translational repression, and play a key role in the regulation of gene expression.  Better understanding of the expression pattern of miRNAs in diseases may improve our understanding of the biological basis of the disease and identify potential biomarkers. The role of miRNAs in primary Sjögren’s syndrome (PSS) and PSS-related lymphoma remains poorly understood. The aim of this project is to identify a miRNA signature for PSS-related lymphoma.

Methods

We profiled the expression of miRNAs in whole blood (PaxGene) total RNA preparations using the Exiqon miRCURY LNA array which encompasses >1400 miRNAs and other small non-coding RNAs. A discovery cohort comprised of 36 samples from the United Kingdom Primary Sjögren’s Syndrome Registry (UKPSSR) (12 PSS patients with lymphoma, 12 PSS patients without lymphoma, 12 healthy controls) were used in the initial analysis. We also explored different normalisation strategies and developed an approach which we considered most appropriate for analysing these data. Real-Time PCR was used to validate the most highly differentially expressed miRNAs between groups. A miRNA signature for PSS-related lymphoma was identified using cluster analysis followed by validation with a second independent cohort of 36 patients and controls. 

Results

The initial miRNA array profiling revealed a clear clustering of the 3 subject groups. Between the ‘High Function’ and ‘Lymphoma’ patient groups, 44 miRNAs were found to be differentially expressed. The differential expressions of these miRNA were validated by RT-PCR in 3 out of 9 miRNAs with the highest fold-changes between the two groups. Indeed, based on the expression levels of these 3 miRNAs were sufficient to distinguish PSS patients with lymphoma from those without. Two out of these 3 miRNAs were also differentially expressed between the same two groups in the validation cohort. 

Conclusion

We have identified 2 miRNAs that are differentially expressed in peripheral blood between PSS patients with lymphoma and those without lymphoma. Identifying the mRNA targets of these miRNAs in PSS may improve our understanding of the pathogenesis of PSS-related lymphoma. Furthermore, miRNAs may be useful biomarkers for PSS-related lymphoma.

Disclosure:

J. Tarn,
None;

S. Cockell,
None;

C. Gillespie,
None;

S. Al-Ali,
None;

K. James,
None;

J. Locke,
None;

S. Bowman,
None;

B. Griffiths,
None;

D. Young,
None;

W. F. Ng,
None.

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