Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with psoriasis

Abstract

Background Psoriatic arthritis (PsA) develops in~30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non-coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation. Objectives To explore whether plasma-derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis. Methods Plasma samples were obtained from patients with cutaneous-only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY TM Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis. Results RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let-7b-5p and miR-30e-5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53-0.83) for let-7b-5p and 0.69 (95% CI 0.55-0.84) for miR-30e-5p. Conclusions Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients.

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review

“…Of those 14 markers, six showed a positive association with the presence of PsA in Pso: the presence of anti-citrullinated protein antibodies (ACPA) [ 37 – 40 ], a higher level of IL-34 [ 56 , 66 ], a higher level of tumor necrosis factor alpha (TNFα) [ 56 , 64 ], a higher mean platelet volume (MPV) [ 68 , 69 ], a higher LDL:HDL ratio [ 62 , 64 , 71 , 76 ], and the presence of microRNA miR-146a-50 [ 78 , 79 ].…”

Analysis of extracellular vesicle mRNA derived from plasma using the nCounter platform

“…Here, we present a workflow for nCounter-based analysis of plasma-derived EVs and we demonstrate that it can be used to efficiently detect transcripts in EV-enriched preparations from cancer patients and control samples. The first step of the workflow is plasma processing using the precipitation-based miRCURY kit which, as previously described 29,30 , yielded pellets enriched in EVs. Clinical laboratories do not usually have access to ultracentrifugation and precipitation kits offer several advantages, such as short turn-around time and limited technical requirements.…”

Extracellular Vesicles as Potential Therapeutics for Inflammatory Diseases

“…Many studies have shown that endothelial and platelet-derived EVs are elevated in patients with psoriasis [ 50 , 51 , 52 ]. Recently, potential biomarkers of psoriasis are being discovered through miRNA profiling analysis of plasma-derived EVs [ 53 , 54 ]. AD, one of the eczemas, is another common chronic inflammatory skin disease.…”