Role of miRNA-21-5p As a Potential Biomarker for the Inflammation Pathway in Psoriatic Disease and Response to Methotrexate Treatment

Rohan Machhar¹, Justine Y. Ye², Vinod Chandran² and Dafna D Gladman³, ¹University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ²Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ³Toronto Psoriatic Arthritis Research Program, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Inflammation, MicroRNA, psoriatic arthritis and treatment

Session Information

Date: Tuesday, October 23, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Basic Science Poster

Session Type: ACR Poster Session C

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

Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory arthritis occurring in patients with psoriasis. miRNAs are small non coding RNAs whose main function, at a post transcriptional level, is to modulate the expression of target genes via translation inhibition or mRNA degradation. Several studies have shown links between altered miRNA expression with the pathogenesis of several autoimmune disorders. We demonstrated earlier that miR-21-5p was upregulated in PsA and psoriasis without arthritis (PsC) compared to healthy controls (HC) (p<0.001), thus a potential biomarker for PsA. We aimed to determine whether miR-21-5p modulates inflammation in psoriatic disease (PsD = PsA & PsC) through IL-17/IL-23 axis, and determine its role in the treatment response to methotrexate (MTX).

Methods: Serum & whole blood RNA samples were collected from 40 patients with early PsA (<2 years’ disease duration and not receiving biologic therapy), 40 patients with psoriasis who have been confirmed by rheumatologist not to develop PsA (PsC >10 years disease duration, not receiving biologic therapy, and matched to PsA patients on age, sex, psoriasis duration, and age of psoriasis onset), and 42 HC (matched to patients based on age, sex). RNA was extracted using the Tempus Spin RNA Isolation Kit. miR-21-5p was validated using droplet digital PCR (ddPCR). miR-21-5p expression was also measured in 30 PsA patients before and after 24 weeks of MTX treatment. Serum levels of IL-17, IL-23, TGFβ1 and CXCL10 were measured by ELISAs from R&D Biosystems kits as per protocols. Descriptive statistics are provided, Spearman correlations were performed.

Results: miR-21-5p was significantly down regulated 24 weeks post-MTX treatment in 30 patients (p< 0.008), the levels of expression correlated with the actively inflamed joint counts (r=0.897, p=<0.0001). IL-17 levels in PsA & PsC were significantly different from HC (p= 0.031), but not different between PsA & PsC. IL-17 levels were down- regulated post treatment and correlated with miR-21-5p (r=0.559, p= 0.0002), CXCL10 levels (r=0.485, p=0.013), IL-23 levels (r=0.429, p=0.02) and negatively correlated with TGFβ1 (r= -0.449, p=0.038).

Conclusion: In the presence of increased levels of miR-21-5p, IL-17 and IL-23 are upregulated while TGFβ1 is down regulated. When miR-21-5p is decreased IL-17 and IL-23 downregulate, with up regulation of TGFβ1. We have thus determined the role of miR21-5p as a biomarker for inflammation pathway in psoriatic disease and response to methotrexate possibly through modulation of CXCL10 and IL-17.

Table 1: Demographic, clinical and relative expression data
Variable	PsA ( N=40)	PsC (N=40)	HC (N=42)	P Value
miR-21-5p	122.7 (93.1)	58.5 (36.0)	11.5 (9.6)	<0.001
IL-17	0.5(0.2)	0.5 (0.0)	0.4(0.1)	0.031
Sex Male Female	16 (40%) 24 (60%)	15 (38%) 25 (63%)	15 (38%) 25 (63%)	0.96
Age	40.7 (11.0)	41.9 (11.0)	43.8 (12.0)	0.96
PASI	7.1 (10.8)	6.2 (4.4)	N/A	0.61
AJTOT	6.4 (7.0)	11.0 (.)	N/A	0.52
CRP_p, n (%)	6 (15%)	1 (3%)	N/A	0.048
PASI-psoriasis areas severity index; AJTOT-total actively inflamed joint count; CRP-C reactive protein; PsA – psoriatic arthritis;; PsC – cutaneous psoriasis without arthritis; HT- healthy cotnrols

Table 2: Spearman Correlation Coefficients, N=30 Prob > |r| under H0: Rho=0

miR-21-5p

IL-17

IL-23

TGFβ1

CXCL10

IL-17

r=0.559,

p= 0.0002

1.00000

r=0.429, p=0.02

r=-0.449, p=0.038

r=0.485, p=0.013

AJTOT

r=0.897, p=<0.0001

r=0.415

p=0.0153

r=0.459

p=0.0376

r=-0.075

p=0.7131

r=0.109

p=0.641

r=0.492

p=0.0027

r=0.329

p=0.0365

r=0.221

p=0.4135

r=-0.189

p=0.5042

r=0.076

p=0.9154

r=0.407

p=0.0151

r=0.386

p=0.0312

r=0.461

p=0.0342

r=-0.174

p=0.6025

r=0.106

p=0.7874

DAPSA

r=0.354

p=0.034

r=0.493

p=0.0048

r=0.513

p=0.0281

r=-0.195

p=0.5418

r=0.328

p=0.421

AJTOT-total actively inflamed joint count; SJ-swollen joint count; TJ- Tender Joint count; DAPSA-Disease activity in Psoriatic arthritis score

Disclosure: R. Machhar, None; J. Y. Ye, None; V. Chandran, AbbVie Inc., 2,AbbVie Inc., amgen, celgene, eli lilly, Janssen, Novartis, Pfizer and UCB, 5,Eli Lilly and Co., 9; D. D. Gladman, Abbvie, Amgen, BMS, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB, 5,Abbvie, Amgen, Celgene, Janssen, Novartis, Pfizer and UCB, 2.

To cite this abstract in AMA style:

Machhar R, Ye JY, Chandran V, Gladman DD. Role of miRNA-21-5p As a Potential Biomarker for the Inflammation Pathway in Psoriatic Disease and Response to Methotrexate Treatment [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/role-of-mirna-21-5p-as-a-potential-biomarker-for-the-inflammation-pathway-in-psoriatic-disease-and-response-to-methotrexate-treatment/. Accessed .

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