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Updated: Nov 11, 2025

Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension
Dirk M Wuttge1, Anting L Carlsen2, Gabriel Teku3
1Department of Clinical Sciences Lund, Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
Objectives:
SSc-associated pulmonary arterial hypertension (SSc-APAH) is a late but devastating complication of SSc. Early identification of SSc-APAH may improve survival. We examined the role of circulating miRNAs in SSc-APAH.
Methods:
Using quantitative RT-PCR the abundance of mature miRNAs in plasma was determined in 85 female patients with ACA-positive lcSSc. Twenty-two of the patients had SSc-APAH. Sixty-three SSc controls without PAH were matched for disease duration. Forty-six selected miRNA plasma levels were correlated with clinical data. Longitudinal samples were analysed from 14 SSc-APAH and 27 SSc patients.
Results:
The disease duration was 12 years for the SSc-APAH patients and 12.7 years for the SSc controls. Plasma expression levels of 11 miRNAs were lower in patients with SSc-APAH. Four miRNAs displayed higher plasma levels in SSc-APAH patients compared with SSc controls. There was significant difference between groups for miR-20a-5p and miR-203a-3p when correcting for multiple comparisons (P = 0.002 for both). Receiver operating characteristics curve showed AUC = 0.69-0.83 for miR-21-5p and miR-20a-5p or their combination. miR-20a-5p and miR-203a-3p correlated inversely with NT-pro-Brain Natriuretic Protein levels (r = -0.42 and -0.47). Mixed effect model analysis could not identify any miRNAs as predictor of PAH development. However, miR-20a-5p plasma levels were lower in the longitudinal samples of SSc-APAH patients than in the SSc controls.
Conclusions:
Our study links expression levels of the circulating plasma miRNAs, especially miR-20a-5p and miR-203a-3p, to the occurrence of SSc-APAH in female patients with ACA-positive lcSSc.
Insights
Circulating microRNAs (miRNAs) in plasma may help identify SSc-associated pulmonary arterial hypertension (SSc-APAH). Specific miRNAs, like miR-20a-5p and miR-203a-3p, show altered levels in patients with SSc-APAH, potentially aiding early diagnosis.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Molecular Biology
- Genetics
Background:
- Scleroderma (SSc) can lead to pulmonary arterial hypertension (SSc-APAH), a serious complication.
- Early detection of SSc-APAH is crucial for improving patient survival rates.
- Circulating microRNAs (miRNAs) are being investigated as potential biomarkers for diseases.
Purpose of the Study:
- To investigate the role of circulating miRNAs in the development of SSc-APAH.
- To identify specific miRNAs that can serve as early diagnostic markers for SSc-APAH.
Main Methods:
- Quantitative RT-PCR was used to measure mature miRNA abundance in plasma from 85 female patients with ACA-positive limited cutaneous SSc (lcSSc).
- Patients were divided into SSc-APAH (n=22) and SSc control (n=63) groups, matched for disease duration.
- Plasma miRNA levels were correlated with clinical data, and longitudinal samples were analyzed.
Main Results:
- Eleven miRNAs showed lower plasma levels, and four showed higher levels in SSc-APAH patients compared to controls.
- miR-20a-5p and miR-203a-3p levels were significantly different between groups (P=0.002) and correlated inversely with NT-pro-Brain Natriuretic Protein.
- Receiver operating characteristic analysis indicated potential diagnostic value for miR-21-5p and miR-20a-5p, individually or combined (AUC 0.69-0.83).
Conclusions:
- Circulating plasma miRNAs, particularly miR-20a-5p and miR-203a-3p, are linked to the occurrence of SSc-APAH in female patients with ACA-positive lcSSc.
- These miRNAs may serve as valuable biomarkers for early SSc-APAH detection.
- Further research is warranted to validate these findings and explore their clinical utility.

