In this doctoral dissertation, we investigated the pathogenic, diagnostic, and prognostic significance of regulatory short non-coding microRNA (miRNA) molecules in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The multifactorial pathogenesis of tissue injury in AAV is primarily driven by loss of tolerance to self-antigens, manifested by the presence of pathogenic antineutrophil autoantibodies (ANCA), which serve as established biomarkers. ANCA levels not only have diagnostic value but also possess a degree of prognostic relevance. We hypothesized that, alongside genetic and environmental factors, specific miRNAs play a role in AAV pathogenesis, and owing to their stability in serum samples, they may serve as potential non-invasive disease biomarkers.
The fundamental morphological feature of AAV is an autoimmune necrotizing small vessel vasculitis, frequently involving the kidneys in the form of crescentic glomerulonephritis (AAV-GN), which substantially influences morbidity and mortality in affected patients. Disease-specific miRNAs in the context of renal involvement in AAV have not been comprehensively characterized, as prior studies have been limited by small sample sizes, restricted panels of preselected miRNAs, and lack of correlation with clinical and histopathological indicators of AAV-GN activity, as well as absent comparative tissue-serum expression analyses of specific miRNAs.
Therefore, our study focused on identifying and validating altered expression profiles of specific miRNAs indicative of active AAV-GN. and examining their tissue-serum expression correlations. Furthermore, we assessed whether miRNA expression profiles could distinguish serologically defined AAV subgroups, namely PR3-ANCA and MPO-ANCA positive patients, consistent with the recognized heterogeneity of AAV and the known associations between ANCA serotype, genetic markers, and clinical phenotypes.
|
