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Published on: October 27, 2023
Circulating microRNAs as potential biomarkers of disease activity and structural damage in ankylosing spondylitis
Carlos Perez-Sanchez1,2,3, Pilar Font-Ugalde1,2,3, Patricia Ruiz-Limon1,2,3
1Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba 14004, Spain.
Abstract:
Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of microRNA (miR)-146a-5p, miR-125a-5p, miR-151a-3p and miR-22-3p, and lower expression of miR-150-5p, and miR-451a were found in AS versus healthy donors. Interestingly, higher miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p and miR-451a expression was also observed in AS than psoriatic arthritis patients. The areas under the curve, generated to assess the accuracy of microRNAs as diagnostic biomarkers for AS, ranged from 0.614 to 0.781; the six-microRNA signature reached 0.957. Bioinformatics analysis revealed that microRNAs targeted inflammatory and bone remodeling genes, underlying their potential role in this pathology. Indeed, additional studies revealed an association between these six microRNAs and potential target proteins related to AS pathophysiology. Furthermore, miR-146a-5p, miR-125a-5p and miR-22-3p expression was increased in active versus non-active patients. Moreover, miR-125a-5p, miR-151a-3p, miR-150-5p and miR-451a expression was related to the presence of syndesmophytes in AS patients. Overall, this study identified a six-plasma microRNA signature that could be attractive candidates as non-invasive biomarkers for the AS diagnosis, and may help to elucidate the disease pathogenesis.
Insights
This study identifies six plasma microRNAs as potential biomarkers for early diagnosis of ankylosing spondylitis (AS). These microRNAs may also help understand AS disease mechanisms and progression.
Area of Science:
- Biochemistry
- Genetics
- Immunology
Background:
- Ankylosing spondylitis (AS) diagnosis is challenging before irreversible joint damage occurs.
- Circulating microRNAs show promise as diagnostic biomarkers for various diseases.
- Identifying early diagnostic markers for AS is crucial for timely intervention.
Purpose of the Study:
- To identify circulating plasma microRNAs as potential biomarkers for ankylosing spondylitis (AS).
- To investigate the association of these microRNAs with AS disease activity and features.
- To explore the role of these microRNAs in AS pathogenesis.
Main Methods:
- Analysis of plasma microRNA expression profiles in AS patients, psoriatic arthritis patients, and healthy donors.
- Utilizing bioinformatics to predict microRNA targets and pathways.
- Correlating microRNA expression with clinical parameters like disease activity and syndesmophyte presence.
Main Results:
- A distinct signature of six plasma microRNAs (miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p, miR-150-5p, and miR-451a) differentiated AS patients from healthy controls and psoriatic arthritis patients.
- This six-microRNA signature achieved a high diagnostic accuracy (AUC 0.957).
- Bioinformatics and protein association studies suggested these microRNAs target inflammatory and bone remodeling genes relevant to AS.
Conclusions:
- A six-plasma microRNA signature shows potential as a non-invasive biomarker for AS diagnosis.
- These microRNAs may play a role in AS pathogenesis, influencing inflammation and bone remodeling.
- MicroRNA expression levels correlate with AS disease activity and radiographic features like syndesmophytes.
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