Aetiopathogenesis
Acetylcholinesterase-associated inflammation in patients with giant cell arteritis. Evaluation by histology and 11C-donepezil PET/CT
P. Therkildsen1, B.D. Nielsen2, I.T. Hansen3, K.K. Keller4, T. Steiniche5, L.C. Gormsen6, P. Borghammer7, E.-M. Hauge8
- Department of Rheumatology, Aarhus University Hospital, Denmark.
- Department of Rheumatology and Department of Clinical Medicine, Aarhus University Hospital, Denmark.
- Department of Rheumatology and Department of Clinical Medicine, Aarhus University Hospital, Denmark.
- Department of Rheumatology, Aarhus University Hospital, Denmark.
- Department of Clinical Medicine and Department of Histopathology, Aarhus University Hospital, Denmark.
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Denmark.
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Denmark.
- Department of Rheumatology and Department of Clinical Medicine, Aarhus University Hospital, Denmark. ellen.hauge@aarhus.rm.dk
CER11754
2019 Vol.37, N°2 ,Suppl.117
PI 0020, PF 0025
Aetiopathogenesis
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PMID: 31162030 [PubMed]
Received: 19/09/2018
Accepted : 17/12/2018
In Press: 21/05/2019
Published: 21/05/2019
Abstract
OBJECTIVES:
To investigate the in-situ expression of acetylcholinesterase (AChE) in the inflamed vessel wall of patients with biopsy-positive giant cell arteritis (GCA) as compared to biopsy-negative non-GCA patients, and to evaluate the in-vivo expression of AChE in patients with large-vessel GCA (LVGCA) by 11C-donepezil (AChE inhibitor) positron emission tomography/computed tomography (PET/CT).
METHODS:
Twenty-four biopsy-positive GCA and 44 biopsy-negative non-GCA patients were included for AChE histology. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and the AChE expression were assessed by an experienced pathologist on a 3-point scale. Two patients with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) PET/CT verified LVGCA were included for 11C-donepezil PET/CT. PET images were assessed by an experienced nuclear medicine physician.
RESULTS:
AChE was expressed in all 24 positive temporal artery biopsies, 10/24 showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media smooth muscle cells (grade 0) in any of the biopsy-negative non-GCA patients. The AChE expression was in 86% agreement with the histological inflammation. The AChE expression was not associated with any clinical or biochemical findings. In both LV-GCA patients, PET/CT revealed extensive vascular FDG uptake but no 11C-donepezil uptake.
CONCLUSIONS:
AChE is highly expressed in the inflamed vessel wall of patients with GCA. Although, 11C-donepezil PET/CT showed no vascular uptake in the FDG PET/CT verified LV-GCA patients, histological findings raise the possibility that AChE can be used in the development of new diagnostic and disease monitoring tools for GCA.
