Author/Editor		Jurčić, Vesna; Bolha, Luka; Matjašič, Alenka; Sedej, Ivana; Dolinar, Ana; Grubelnik, Gašper; Hauptman, Nina; Pižem, Jože; Jevšinek Skok, Daša; Hočevar, Alojzija; Ravnik-Glavač, Metka; Glavač, Damjan
Title		Association between histopathologic changes and expression of selected microRNAs in skin of adult patients with IgA vasculitis
Type		članek
Publication year		2019
Volume		str. str.
ISSN		0309-0167 - Histopathology
Language		eng
Abstract		Aims Immunoglobulin A vasculitis (IgAV) is a common small-vessel systemic vasculitis, histologically characterized by granulocyte infiltration and IgA deposition in vessel walls. Information on microRNA (miRNA) involvement in IgAV is limited. The aim of the study was to analyse the association between histopathologic changes and expression profiles of 14 miRNAs in the affected skin of 70 adult patients with IgAV. Methods and results miRNA expression analysis was performed by quantitative real-time PCR and evaluation of histopathologic changes by light and immunofluorescence microscopy on formalin-fixed, paraffin-embedded skin excision samples. In IgAV-affected skin, granulocyte infiltration was significantly associated with vessel fibrinoid necrosis. Of the analysed miRNAs, 4 exhibited increased expressions by 2-fold (let-7d/-7f, miR-21-5p/-203-3p), 5 by 5-fold (let-7b, miR-17-5p/-155-5p/-423-5p/-451a) and 3 by 15-fold (let-7a, miR-21-3p/-223-3p), compared to the controls (all p < 0.001). miR-146a-5p and miR-148b-3p showed 3-fold decreased expression (p = 0.981 and p < 0.001). The expression of miR-223-3p also showed a significant positive association with granulocyte infiltration and fibrinoid necrosis. Conclusions Altered miRNA expression, especially miRNA-223-3p, may associate with the skin inflammatory state in IgAV. The majority of aberrantly expressed miRNAs in IgAV-affected skin are known to influence the NF-[keta]B signalling pathway, crucial for activation of key pro-inflammatory genes, including TNF-[alpha], IL-6 and IL-8. Furthermore, miR-146a-5p and miR-148b-3p, negative regulators of inflammatory gene expression, showed decreased expression and could contribute to the exaggerated inflammation. Further investigation of miRNAs expression in the affected tissues could improve knowledge of IgAV pathogenesis and possibly help to identify novel biomarkers in body fluids.
Keywords		IgA vasculitis histopathology skin IgA vaskulitis histopatologija koža