ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2804

The Global miRNA Whole Blood Profile of Ankylosing Spondylitis

Carolina Mejia Otero1, Shervin Assassi1, Michael H. Weisman2, Michael M. Ward3, Lianne S. Gensler4, Matthew A. Brown5, Minghua Wu1, John Hagan6, John D. Reveille7 and Gloria Salazar1, 1Rheumatology, University of Texas Medical School at Houston, Houston, TX, 2Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, 3NIH/NIAMS, Bethesda, MD, 4Medicine/Rheumatology, University of California, San Francisco, San Francisco, CA, 5The University of Queensland Diamantina Institute, Brisbane, Australia, 6Neurosurgery, University of Texas at Houston, Houston, TX, 7Internal Medicine/Rheumatology, University of Texas Medical School at Houston, Houston, TX

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Tuesday, November 10, 2015

Title: Spondylarthropathies and Psoriatic Arthritis Pathogenesis, Etiology Poster I

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

MicroRNA (miRNA) are small non-coding RNAs that play an important role in posttranscriptional gene regulation and their involvement in the pathophysiology of several autoimmune diseases has been proposed. The role of miRNA in Ankylosing spondylitis (AS) has not been well studied. Recent advances in quantitative polymerase chain reaction (qPCR) allow simultaneous measurement of hundreds of miRNAs. The objective of this study is to use this technology to identify differentially expressed whole blood miRNA in AS patients compared to healthy controls. We hypothesize that AS patients have a distinct whole blood miRNA profile that has potential predictive and pathophysiological significance. 

Methods:

We investigated the miRNA profile in AS whole blood compared to controls using a multiplex qPCR platform. We obtained whole blood samples from 10 AS patients from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort and 10 age-, gender- and ethnicity matched unaffected controls. All patients met modified New York Criteria for AS. Blood was obtained at each study visit for disease activity, genetic markers.Total RNA was isolated using PAXgene blood miRNA kit and examined by Exiqon LNA-enhanced miRNA qPCR platforms. Levels of 752 miRNAs were determined. Patient and control sample miRNA levels were compared using univariate t-test at p<0.05. In this hypothesis generating study, a correction for multiple comparisons was not performed.  

Results:

Whole blood profiling of miRNA revealed a list of 20 miRNA with differential expression in AS patients (table 1). Interestingly the main finding was the high expression of miR-204-5p (12 fold higher than controls, p 0.004). This miRNA has been described particularly in the oncology literature (dysregulation was observed in colon, gastric and pancreatic cancer). Studies in this field show an important role as a regulator of autophagy pathways. Considering the recent discovery of the importance that autophagy pathways play in the pathophysiology of AS this miRNA might play an important role in the pathogenesis of AS.

Conclusion:

AS patients have a whole blood miRNA “signature” based on specific dysregulated miRNA compared to healthy controls. In our study, we found that there is a high expression of miR-204-5p in AS patients compared to controls and this could have implications in the pathophysiology of AS. MiRNA analysis of a larger study population is required to further characterize potential epigenetic factors that may have a role in AS susceptibility. 

Table 1. Dysregulated miRNA in Ankylosing Spondylitis patients compared to healthy controls.

 

miRNA

Location

Fold change

p

1

miR-204-5p

9q21.12

12.45

0.004

2

miR-432-3p

14q32.2

4.08

0.010

3

miR-513a-5p

xq27.3

0.75

0.014

4

miR-200c-3p

12p13.31

0.69

0.019

5

miR-373-5p

19q13.42

0.39

0.022

6

miR-654-5p

14q32.31

4.49

0.025

7

miR-28-3p

3q28

1.45

0.026

8

miR-1911-3p

xq23

2.76

0.027

9

miR-210

11p15.5

0.57

0.029

10

miR-141-3p

12p13.31

0.29

0.030

11

miR-421

xq13.2

0.75

0.030

12

miR-504

xq26.3

2.35

0.032

13

miR-340-5p

5q35.3

0.54

0.037

14

miR-187-3p

18q12.2

3.24

0.039

15

miR-875-3p

8q22.2

0.94

0.039

16

miR-595

7q36.3

0.68

0.042

17

miR-93-5p

7q22.1

0.57

0.044

18

miR-33b-5p

22q13.2

0.45

0.044

19

miR-638

19p13.2

0.51

0.045

20

miR-146a-3p

5q34

2.52

0.047

Disclosure: C. Mejia Otero, None; S. Assassi, None; M. H. Weisman, None; M. M. Ward, None; L. S. Gensler, Amgen, 5,Janssen Pharmaceutica Product, L.P., 5,UCB, 5,Celgene, 9; M. A. Brown, Abbvie, Pfizer, UCB, Wyeth, Leo Pharma, NIAMS, NHMRC, Arthritis Australia, Qld Government, 2,Pfizer, Abbvie, UCB, 5,Pfizer, Abbvie, UCB, 8; M. Wu, None; J. Hagan, None; J. D. Reveille, None; G. Salazar, None.

To cite this abstract in AMA style:

Mejia Otero C, Assassi S, Weisman MH, Ward MM, Gensler LS, Brown MA, Wu M, Hagan J, Reveille JD, Salazar G. The Global miRNA Whole Blood Profile of Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-global-mirna-whole-blood-profile-of-ankylosing-spondylitis/. Accessed .

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