Background/Purpose: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoantibody production, immune complex deposition, and heterogeneous clinical manifestations affecting many organs, including the skin, joints, the central nervous system, and the kidneys. Once clinical symptoms have developed, prompt diagnosis and proper management of SLE remain great challenges to physicians. Due to the heterogeneity of immune dysregulation, the severity and progression of the disease largely varies among patients, while no single biomarker has emerged as a surrogate for disease activity or severity of SLE.
Recently, evidence indicates that exosomes play important roles in immune modulation and are associated with the immune pathogenesis of autoimmune diseases, including systemic lupus erythematosus. Exosomes are 20-150 nm-sized vesicles that function as a vital medium for cellular communication. It encapsulates microRNAs (miRNAs), a non-coding RNA, which are known as gene expression modulators, and strongly relates to physiological conditions like disease status. Here, we have developed a mass-producible and sterilizable nanowire-based device (nanowire device) that can extract urinary exosomal microRNAs efficiently. Our objective of the research is to extract urinal exosomes and detect microRNAs using nanowire devices, and identify biomarkers which could support SLE diagnosis and identify its status and severity.

Methods: Exosomes were extracted by nanowire device and miRNA expression was measured from urine samples of 30 SLE patients and 30 non-SLE donors using a microarray to yield comprehensive microRNA expression profiles.

Results: Differential expression analysis revealed 242 biomarker miRNAs candidates,160 up-regulated and 82 down-regulated in SLE patients compared with healthy individuals. Down-regulation patterns were related to the severity of the disease, revealing severity-specific miRNAs.Pathway analyses revealed the candidate miRNAs showed relation with genes strongly related to SLE including JAK-STAT and BCL pathways. Moreover, we adopted a support vector machine model and successfully developed a classifier to detect SLE based on these miRNA expression patterns, which showed remarkably high sensitivity (0.89) and specificity (0.82).

Conclusion: These findings show that urinary miRNAs may provide insights into SLE pathogenesis, and could be a potential biomarker of disease activity, paving the way to a liquid biopsy for individualized SLE treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-micrornas-as-systemic-lupus-erythematosus-biomarkers-and-its-potential-for-accurate-assessment-of-disease-severity/