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Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
Uncovering mirnomes of patients with interstitial lung diseases and an underlying autoimmune process
Olga Sánchez-Pernaute1,2, Yolanda Benítez3,4,5, Cristina Vadillo Font6
1Rheumatology Department, Unit for Systemic Autoimmune Diseases, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain. osanchezper@unav.es.
Abstract:
Interstitial lung disease (ILD) is a major manifestation of systemic autoimmune rheumatic diseases (SARD). Unmet needs in this population are the early identification of patients at risk of functional deterioration and tailoring therapies on a pathophysiological basis. The study of microRNA is being applied to trace pathogenetic mechanisms and as predictive tool in complex diseases. We have performed bulk small-RNA sequencing in sera from 24 patients with SARD-associated ILD and 5 healthy subjects, in order to identify differentially expressed molecules in the patients and in disease subgroups. Variables of the study included disease duration, radiographic patterns, clinical diagnosis, alterations in nailfold capillaroscopy, functional status, levels of Krebs von den Lungen 6 (KL-6), presence of rheumatoid factor, and outcomes over the following 18-month period. The patients showed 13 differentially expressed miRNA, out of which Let-7i-5p associated with higher KL-6 levels, whereas miR-151a-5p was increased during early disase and miR-483-5p was higher in patients with microvascular involvement. The latter subgroup displayed a specific signature, characterized by the up-regulation of the miR-320 and miR-10 families. Also to underscore was the value of miR-223, miR-142-5p, miR-145-5p, miR-23a-5p, miR-29a-3p, miR-320c, miR-320d and miR-10a-3p in forecasting a progressive phenotype. Functional analysis pointed to an up-regulation of profibrotic miRNA as early biomarkers of poor outcome. On the whole, our data uncover for the first time miRNomes associated to SARD-ILD in an exporatory approach. Whether or not the miRNA shown up in this study applies to the whole population of SARD-ILD warrants confirmation in further research.
Insights
This study identifies specific microRNAs (miRNAs) in patients with systemic autoimmune rheumatic diseases-associated interstitial lung disease (SARD-ILD). These miRNAs may help predict disease progression and identify patients at risk of functional decline.
Area of Science:
- Rheumatology
- Pulmonology
- Molecular Biology
Background:
- Interstitial lung disease (ILD) is a significant complication of systemic autoimmune rheumatic diseases (SARD).
- Early identification of patients at risk of functional deterioration and tailored therapies are unmet needs in SARD-ILD.
- MicroRNAs (miRNAs) are emerging as potential biomarkers for disease mechanisms and prediction.
Purpose of the Study:
- To identify differentially expressed miRNAs in sera of patients with SARD-ILD compared to healthy controls.
- To explore the association of specific miRNAs with clinical variables, disease progression, and outcomes in SARD-ILD.
- To uncover novel miRNA signatures related to SARD-ILD pathogenesis and prognosis.
Main Methods:
- Bulk small-RNA sequencing was performed on serum samples from 24 SARD-ILD patients and 5 healthy subjects.
- Differential gene expression analysis was conducted to identify significantly altered miRNAs.
- Correlations between miRNA levels and clinical parameters (disease duration, radiographic patterns, KL-6, etc.) were assessed.
Main Results:
- Thirteen differentially expressed miRNAs were identified in SARD-ILD patients.
- Let-7i-5p levels correlated with higher KL-6, miR-151a-5p with early disease, and miR-483-5p with microvascular involvement.
- Specific miRNA signatures (e.g., miR-320, miR-10 families) were associated with microvascular involvement and progressive phenotypes, with profibrotic miRNAs indicating poor outcomes.
Conclusions:
- This study provides the first exploratory insights into miRNomes associated with SARD-ILD.
- Specific miRNAs show potential as early biomarkers for predicting functional deterioration and disease progression in SARD-ILD.
- Further research is needed to validate these findings in larger SARD-ILD populations.
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