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.