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Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
Published on: July 8, 2020
MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
Milanka Živanović1, Alojzija Hočevar2,3, Nina Zidar1
1Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Objectives:
To identify aberrantly expressed microRNAs (miRNAs) in sinonasal tissue biopsies of patients with granulomatosis with polyangiitis (GPA), associate their expression profiles to sinonasal histopathology, and assess their differential expression between subgroups of clinically proven GPA patients, healthy controls and patients exhibiting inflammation of other etiology.
Methods:
We included formalin-fixed, paraffin-embedded biopsy tissue samples of sinonasal mucosa from 37 patients with clinically proven GPA, 15 patients with inflammation of other etiology and 14 control patients with normal histology. Of the included GPA patients, 20 patients had characteristic GPA-related histological features, while 17 patients displayed non-specific GPA histopathology in their sinonasal biopsy. Assessment of histological parameters was performed using histopathological techniques, and analysis of miRNA expression with miRCURY LNA miRNA miRNome Human PCR Panels and quantitative real-time PCR.
Results:
We determined expression of 306 miRNAs in sinonasal biopsy samples, which displayed different extent of dysregulation between individual patient groups. Based on their potential to discriminate between the controls, non-GPA and GPA patient subgroups, dysregulation of 11 miRNAs was further assessed, of which miR-1-3p/-21-3p/-93-5p/-155-5p/-1248/-31-3p/-182-5p/-183-5p and let-7b-5p held the potential to stratify patients based on their sinonasal tissue miRNA profile. Notably, several of these miRNAs were associated with the presence of granulomas, vasculitis and necrosis in sinonasal biopsies of GPA patients.
Conclusion:
Our study identifies novel miRNAs putatively implicated in the pathogenesis of GPA, and highlights dysregulated miRNAs as supporting biomarkers in establishing GPA diagnosis, particularly in the early phases of the disease, or in patients with atypical GPA presentation.
Insights
This study identified novel microRNAs (miRNAs) in sinonasal tissue that may play a role in granulomatosis with polyangiitis (GPA). These dysregulated miRNAs could serve as biomarkers for diagnosing GPA, especially in early or atypical cases.
Area of Science:
- Immunology
- Genetics
- Pathology
Background:
- Granulomatosis with polyangiitis (GPA) is a complex autoimmune disease affecting small blood vessels.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various diseases.
- Understanding miRNA dysregulation in GPA sinonasal tissue is crucial for diagnosis and understanding pathogenesis.
Purpose of the Study:
- To identify aberrantly expressed miRNAs in sinonasal tissue biopsies from GPA patients.
- To correlate miRNA expression profiles with sinonasal histopathology.
- To differentiate miRNA expression between GPA subgroups, other inflammatory conditions, and healthy controls.
Main Methods:
- Analysis of formalin-fixed, paraffin-embedded sinonasal mucosa biopsies from 37 GPA patients, 15 with other inflammatory conditions, and 14 controls.
- Histopathological assessment of sinonasal biopsy features.
- miRNA expression profiling using miRCURY LNA miRNA miRNome Human PCR Panels and quantitative real-time PCR.
Main Results:
- Expression of 306 miRNAs was analyzed, revealing dysregulation across patient groups.
- Eleven miRNAs (miR-1-3p, miR-21-3p, miR-93-5p, miR-155-5p, miR-1248, miR-31-3p, miR-182-5p, miR-183-5p, let-7b-5p) showed potential for patient stratification.
- Several identified miRNAs were associated with GPA-specific histopathological features like granulomas, vasculitis, and necrosis.
Conclusions:
- Novel miRNAs implicated in GPA pathogenesis were identified.
- Dysregulated miRNAs show promise as supporting biomarkers for GPA diagnosis, particularly in early or atypical presentations.
- This research contributes to understanding GPA pathophysiology and diagnostic strategies.
