69. Interrelation Between Immune-Related microRNA Signature and Inflammatory Histopathological Features of Giant Cell Arteritis
Creators: name: Bolha1, Luka
name: Alojzija Hočevar2, 3
name: Suljič4, Alen
name: Jurčić1, Vesna
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Inflammation-driven thickening of arterial wall is a typical feature of giant cell arteritis (GCA). Nevertheless, there is still a scarcity of in-depth information on the distinct cellular composition of inflammatory infiltrates in temporal artery biopsies (TABs) from GCA patients, including their immune-related microRNA (miRNA) signatures, which may significantly differ between patients and lead to different clinical outcomes. The aim of this study was to evaluate the association between the expression signature of selected immune-related miRNAs with quantitatively assessed immune cell subsets comprising inflammatory infiltrate in TABs from patients with GCA, and thus highlight the role of altered miRNA expression in impaired regulation of arterial inflammation in GCA. <strong>Methods:</strong> The study included 46 formalin-fixed, paraffin-embedded TABs from clinically diagnosed treatment-naïve patients fulfilling the American College of Rheumatology 1990 classification criteria, including 30 histologically positive and 16 negative GCA TABs. Non-GCA controls included 22 histologically negative TABs from age-matched patients with refuted clinical suspicion of GCA. Quantitative assessment of histological parameters was performed using histopathological and immunohistochemical techniques, and miRNA expression analysis by quantitative real-time PCR. Computational analyses were performed by employing the miRDB database and the STRING online prediction tool. <strong>Results:</strong> Our quantitative histopathological assessment revealed that intense transmural mononuclear inflammatory infiltrates in TAB-positive GCA arteries predominantly comprised CD3<sup>+</sup>, CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes, CD68<sup>+</sup> macrophages, and variable numbers of CD20<sup>+</sup> B lymphocytes, multinucleated giant cells and eosinophil granulocytes. Overall, the lymphocyte infiltrate fraction was characterized by a strong nuclear overexpression of the nuclear factor of activated T cells, cytoplasmic 1 (NFATC). Moreover, we determined a significant overexpression of pro-inflammatory miRNAs miR-132-3p/-142-3p/-142-5p/-155-5p/-210-3p/-212-3p/-326/-342-5p/-511-5p and a significant under-expression of regulatory immune-related miRNAs miR-30a-5p/-30b-5p/-30c-5p/-30d-5p/-30e-5p/-124-3p in TAB-positive GCA arteries, whose expression levels significantly associated with most evaluated histopathological parameters. Notably, we revealed miR-132-3p/-142-3p/-142-5p/-155-5p/-212-3p/-511-5p as major promoters of arterial inflammation and miR-30a-5p/-30c-5p/-30d-5p as putative regulators of NFATC signaling in TAB-positive GCA arteries. <strong>Conclusions:</strong> Our study demonstrated that an altered pro-inflammatory miRNA signature favors enhanced T cell-driven inflammation and macrophage activity in TAB-positive GCA arteries. Furthermore, dysregulation of several immune-related miRNAs seeto contribute crucially to GCA pathogenesis, through impairing their regulatory activity towards T cell-mediated immune responses driven by the calcineurin (CaN)/NFAT signaling pathway, indicating their therapeutic, diagnostic and prognostic potential. <strong>Disclosures:</strong> None.<br> <br>