Abstract
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.
Highlights
The term anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV)encompasses a group of rare, pathogenically distinct entities that share autoimmune small vessel necrotizing vasculitis as a prominent feature, a condition which results in severe target organ damage
Considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results
Reverse transcription (RT) and the quantification of reference miRNAs as suggested by the manufacturer, a similar expression level among all samples was found in 26/30 AAVs, 10/15 CTRLs and 16/20 patients with GN initially considered for inclusion
Summary
The term anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV)encompasses a group of rare, pathogenically distinct entities that share autoimmune small vessel necrotizing vasculitis as a prominent feature, a condition which results in severe target organ damage. AAV is termed either PR3ANCA-positive (PR3-AAV), MPO-ANCA-positive (MPO-AAV) or ANCA-negative The latter encompasses patients with the clinical and pathologic features of ANCA vasculitis without detectable ANCAs. There are several arguments to support this ANCA-based approach, namely the proven in vitro and in vivo pathogenicity of ANCAs and the significant correlation of specific ANCAs with both genetic backgrounds and clinical manifestations. There are several arguments to support this ANCA-based approach, namely the proven in vitro and in vivo pathogenicity of ANCAs and the significant correlation of specific ANCAs with both genetic backgrounds and clinical manifestations The limitations of this approach, and of (over-)relying on ANCAs in general, include: (i) the phenomenon of secondary (“by-stander”) ANCAs in entities other than AAV but with similar clinical presentation; (ii) the possible discordance between serum ANCA titres and disease activity; and (iii) ANCA-negative patients with the clinical and pathologic features of ANCA vasculitis. The latter reportedly accounts for
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