Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis

• Published in: Rheumatology (Oxford, England) England), 2022-07, Vol.61 (7), p.3060-3070
• Main Authors: Esen, Idil, Jiemy, William F, van Sleen, Yannick, Bijzet, Johan, de Jong, Daniel M, Nienhuis, Pieter H, Slart, Riemer H J A, Heeringa, Peter, Boots, Annemieke M H, Brouwer, Elisabeth
• Format: Article
• Language: English
• Subjects: Basic Science; Biomarkers - blood; Carrier Proteins - blood; Chitinase-3-Like Protein 1; Fluorodeoxyglucose F18; Giant Cell Arteritis - diagnostic imaging; Giant Cell Arteritis - pathology; Humans; Inflammation; Leukocyte L1 Antigen Complex; Membrane Proteins - blood; Positron Emission Tomography Computed Tomography; Pyruvate Kinase; Thyroid Hormone-Binding Proteins; Thyroid Hormones - blood
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keab814

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. 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. 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. Conclusion Elevated plasma PKM2 levels reflect active vessel inflammation in GCA and may assist in disease diagnosis and in disease monitoring.