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Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with
L Pasquali1,2, A Svedbom1, A Srivastava1,2
1Dermatology and Venereology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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™ 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.
Insights
Psoriatic arthritis (PsA) diagnosis is challenging. This study found altered levels of extracellular vesicle (EV) microRNAs in PsA patients, suggesting they could be potential biomarkers for arthritis in psoriasis.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Psoriatic arthritis (PsA) affects approximately 30% of psoriasis patients.
- Diagnosing PsA is difficult, lacking reliable molecular markers.
- MicroRNAs within extracellular vesicles (EVs) are circulating regulatory molecules.
Purpose of the Study:
- To investigate plasma-derived EV microRNAs as potential biomarkers for PsA in psoriasis patients.
- To identify specific microRNAs associated with PsA development.
Main Methods:
- Plasma EVs were isolated from patients with psoriasis only (PsC) and those with PsA.
- RNA sequencing identified differentially expressed EV miRNAs in a discovery cohort.
- Quantitative PCR (qPCR) validated selected miRNAs in a larger cohort.
Main Results:
- Nineteen plasma EV miRNAs showed significant differences between PsA and PsC groups in the discovery phase.
- Lower levels of let-7b-5p and miR-30e-5p in plasma EVs were confirmed in PsA patients.
- These decreased miRNA levels were associated with PsA presence, with ROC AUCs of 0.68 and 0.69 respectively.
Conclusions:
- Circulating EV microRNA levels are significantly altered in PsA patients compared to PsC patients.
- The study suggests that EV microRNAs hold promise as diagnostic biomarkers for PsA.
- Further research could establish EV microRNAs as reliable indicators for arthritis in psoriasis.
