18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Large-Vessel Vasculitis During Active and Inactive Disease Stages Is Associated with the Metabolic Profile, but Not the Macrophage-Related Cytokines: A Proof-of-Concept Study
Dimitris Anastasios Palamidas,
Georgios Kalykakis,
Dimitra Benaki,
Loukas Chatzis,
Ourania D. Argyropoulou,
Panagiota Palla,
Antonia Kollia,
Pavlos Kafouris,
Marinos Metaxas,
Andreas V. Goules,
Emmanuel Mikros,
Konstantinos Kambas,
Constantinos D. Anagnostopoulos,
Athanasios G. Tzioufas
Affiliations
Dimitris Anastasios Palamidas
Department of Pathophysiology and Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11526 Athens, Greece
Georgios Kalykakis
Department of Informatics, Ionian University, 49100 Kerkyra, Greece
Dimitra Benaki
Department of Pharmaceutical Chemistry, School of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece
Loukas Chatzis
Department of Pathophysiology and Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11526 Athens, Greece
Ourania D. Argyropoulou
Department of Pathophysiology and Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11526 Athens, Greece
Panagiota Palla
Department of Pathophysiology and Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11526 Athens, Greece
Antonia Kollia
PET-CT Department & Preclinical Imaging Unit, Center for Experimental Surgery, Clinical & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Pavlos Kafouris
PET-CT Department & Preclinical Imaging Unit, Center for Experimental Surgery, Clinical & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Marinos Metaxas
PET-CT Department & Preclinical Imaging Unit, Center for Experimental Surgery, Clinical & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Andreas V. Goules
Department of Pathophysiology and Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11526 Athens, Greece
Emmanuel Mikros
Department of Pharmaceutical Chemistry, School of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece
Konstantinos Kambas
Laboratory of Molecular Genetics, Department of Immunology, Hellenic Pasteur Institute, 11521 Athens, Greece
Constantinos D. Anagnostopoulos
PET-CT Department & Preclinical Imaging Unit, Center for Experimental Surgery, Clinical & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Athanasios G. Tzioufas
Department of Pathophysiology and Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11526 Athens, Greece
Giant cell arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial GCA and large-vessel vasculitis (LV)-GCA, involving the thoracic aorta and its branches. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosing patients with systemic disease. However, its association with soluble inflammatory markers is still elusive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT-positive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The most-diseased-segment target-to-background ratio (TBRMDS) was calculated for 13 LV-GCA patients, while 14 cranial GCA and 14 Polymyalgia Rheumatica patients with negative initial PET/CT scans served as disease controls. Serum macrophage-related cytokines were evaluated by cytometric bead array (CBA). Finally, previously published NMR/metabolomics data acquired from the same blood sampling were analyzed along with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.32 vs. 2.65, p = 0.006). The analysis identified nine serum metabolites as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group but not in the disease controls. Cytokine levels were not associated with PET/CT activity. Combining CRP, ESR, and TBRMDS with choline levels, a composite index was generated to distinguish active and inactive LV-GCA (20.4 vs. 11.62, p = 0.001). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for everyday clinical practice.
