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Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2022 Jul 06; Vol. 61 (7), pp. 3060-3070. - Publication Year :
- 2022
-
Abstract
- Objectives: GCA is a large vessel vasculitis in which metabolically active immune cells play an important role. GCA diagnosis is based on CRP/ESR and temporal artery biopsies (TABs), in combination with 18F-fluorodeoxyglucose ([18F]FDG)-PET/CT relying on enhanced glucose uptake by glycolytic macrophages. Here, we studied circulating Pyruvate Kinase M2 (PKM2), a glycolytic enzyme, as a possible systemic marker of vessel wall inflammation in GCA.<br />Methods: Immunohistochemical detection of PKM2 was performed on inflamed (n = 12) and non-inflamed (n = 4) TABs from GCA patients and non-GCA (n = 9) patients. Dimeric PKM2 levels were assessed in plasma of GCA patients (n = 44), age-matched healthy controls (n = 41), metastatic melanoma patients (n = 7) and infection controls (n = 11). CRP, ESR and macrophage markers calprotectin and YKL-40 were correlated with plasma PKM2 levels. To detect the cellular source of plasma PKM2 in tissue, double IF staining was performed on inflamed GCA TABs. [18F]FDG-PET scans of 23 GCA patients were analysed and maximum standard uptake values and target to background ratios were calculated.<br />Results: PKM2 is abundantly expressed in TABs of GCA patients. Dimeric PKM2 plasma levels were elevated in GCA and correlated with CRP, ESR, calprotectin and YKL-40 levels. Elevated plasma PKM2 levels were downmodulated by glucocorticoid treatment. PKM2 was detected in both macrophages and T cells at the site of vascular inflammation. Circulating PKM2 levels correlated with average target to background ratios PET scores.<br />Conclusion: Elevated plasma PKM2 levels reflect active vessel inflammation in GCA and may assist in disease diagnosis and in disease monitoring.<br /> (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
- Subjects :
- Biomarkers blood
Chitinase-3-Like Protein 1
Fluorodeoxyglucose F18
Humans
Inflammation
Leukocyte L1 Antigen Complex
Positron Emission Tomography Computed Tomography
Pyruvate Kinase
Thyroid Hormone-Binding Proteins
Carrier Proteins blood
Giant Cell Arteritis diagnostic imaging
Giant Cell Arteritis pathology
Membrane Proteins blood
Thyroid Hormones blood
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 61
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 34730794
- Full Text :
- https://doi.org/10.1093/rheumatology/keab814