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Background <p>Giant<!--Query ID="Q1" Text="Please check if article title presented correctly. " Resolved="yes"--> cell arteritis (GCA) is a chronic granulomatous<!--Query ID="Q2" Text="Please check if the authors and their affiliation are presented and indicated correctly. " Resolved="yes"--> 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.</p> Objective <p>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.<!--Query ID="Q3" Text="Please confirm if the author names are presented accurately. " Resolved="yes"--></p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.<!--Query ID="Q4" Text="Please check abbreviation section if the provided description of the corresponding terms are captured correctly. " Resolved="yes"--></p>

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Increased expression of Toll-like receptors and associated alarmins in temporal arteries of patients with giant cell arteritis

  • 期刊论文

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  • 发表日期：

    2025年11月12日

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  • S. Seidlberger,
  • M. Schirmer,
  • G. Wietzorrek,
  • J. A. Jiménez-Heffernan,
  • M. Pardines,
  • M. de las Fuentes Monreal,
  • M. A. González-Gay,
  • S. Castañeda,
  • S. Santos-Sierra

摘要

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.