MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis

ObjectivesTo 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 pat...

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Main Authors: Milanka Živanović, Alojzija Hočevar, Nina Zidar, Metka Volavšek, Luka Bolha
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1579750/full
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author Milanka Živanović
Alojzija Hočevar
Alojzija Hočevar
Nina Zidar
Metka Volavšek
Luka Bolha
author_facet Milanka Živanović
Alojzija Hočevar
Alojzija Hočevar
Nina Zidar
Metka Volavšek
Luka Bolha
author_sort Milanka Živanović
collection DOAJ
description ObjectivesTo 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.
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spelling doaj-art-d50a7db63b314232a6b69ae326889e562025-08-20T02:17:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15797501579750MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitisMilanka Živanović0Alojzija Hočevar1Alojzija Hočevar2Nina Zidar3Metka Volavšek4Luka Bolha5Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaObjectivesTo 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1579750/fullgranulomatosis with polyangiitissinonasal tissuemicroRNAinflammationbiomarker
spellingShingle Milanka Živanović
Alojzija Hočevar
Alojzija Hočevar
Nina Zidar
Metka Volavšek
Luka Bolha
MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
Frontiers in Immunology
granulomatosis with polyangiitis
sinonasal tissue
microRNA
inflammation
biomarker
title MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
title_full MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
title_fullStr MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
title_full_unstemmed MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
title_short MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
title_sort microrna expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis
topic granulomatosis with polyangiitis
sinonasal tissue
microRNA
inflammation
biomarker
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1579750/full
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