@article{10902/38993,
year = {2025},
url = {https://hdl.handle.net/10902/38993},
abstract = {Background: Giant cell arteritis (GCA) is a chronic granulomatous inflammatory disease involving large- and medium-sized arteries. The disease spectrum comprises cranial (C-GCA), extracranial (EC-GCA) and mixed phenotypes. Toll-like receptors (TLRs) in the affected arteries may play an important role in GCA pathogenesis. However, data on TLR and TLR-ligands expression pattern in GCA arteries are lacking.
Objective: To investigate the expression of TLRs and putative ligands in temporal artery biopsies (TAB) from C-GCA, EC-GCA and isolated polymyalgia rheumatica (PMR) patients to establish a link between TLRs, antigen expression, and disease stage. To correlate the plasma levels of identified TLR-ligands with standard inflammatory markers (IL-6, CRP, ESR) in these patients.
Methods: Immunofluorescence staining of TLR2/4/7/8, HMGB-1, SAA, fibrinogen, and p-glycoprotein was performed with TABs of six biopsy proven C-GCA, six EC-GCA, five PMR patients and seven age-matched controls. Association studies among plasma inflammatory markers were done with 139 PMR and 40 GCA patients.
Results: The levels of TLR2/4/7/8 and the alarmins HMGB-1, SAA, and fibrinogen were highly increased in C-GCA TABs in the sites of inflammation and less in EC-GCA TABs. P-glycoprotein was overexpressed in C-GCA TABs. Glucocorticoids or TAK1-inhibitor treatment decreased the fibrinogen- and SAA-mediated IL-6 production in control PBMCs. Plasma levels of SAA and fibrinogen associated strongly with CRP and ESR levels.
Conclusion: TLRs are overexpressed at the site of vascular inflammation in C-GCA and at a lower level in EC-GCA and PMR with negative TAB. Moreover, HMGB-1, SAA, and fibrinogen may serve as disease biomarkers of patients with C-GCA.},
organization = {This research was supported by the Austrian Science Fund (FWF) project P35219-B to SSS. SC was granted by Ministerio de Economía y Competitividad (ISCiii; Grant no. PI21/0147) and cofunded by the European Union. MP has been funded by the program INVESTIGO 2022-C23.I01.P03.S0020-0000031 from the ISCiii and co-funded by the European Union. MAGG research is supported by the Spanish Ministry of Health, Instituto de Salud Carlos III (ISCiii), Spanish Red de Investigación RICORS (RD24/0007/0031).},
publisher = {BioMed Central},
publisher = {Molecular Medicine, 2025, 31(1), 33},
title = {Increased expression of Toll-like receptors and associated alarmins in temporal arteries of patients with giant cell arteritis},
author = {Seidlberger, S. and Schirmer, M. and Wietzorrek, G. and Jiménez Heffernan, J.A. and Pardines, M. and De las Fuentes Monreal, M. and González-Gay Mantecón, Miguel Ángel and Castañeda, S. and Santos Sierra, S.},
}