Diana Ernst1, Desiree Weiberg2, Niklas T Baerlecken3, Wolfgang Schlumberger4, Cornelia Daehnrich4, Reinhold E Schmidt3, Frank M Bengel2, Thorsten Derlin2, Torsten Witte3. 1. Dept. of Rheumatology & Immunology, Hannover Medical University, Carl-Neuberg-Str.1, 30625 Hannover, Germany. Electronic address: ernst.diana@mh-hannover.de. 2. Dept. of Nuclear Medicine, Hannover Medical University, Carl-Neuberg-Str.1, 30625 Hannover, Germany. 3. Dept. of Rheumatology & Immunology, Hannover Medical University, Carl-Neuberg-Str.1, 30625 Hannover, Germany. 4. Euroimmun, Medizinische Labordiagnostika AG, Seekamp 31, 23560 Lübeck, Germany.
Abstract
BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory process of vessel walls responsible for coronary, cerebrovascular and peripheral vascular disease, which together account for the majority of non-infective global deaths. Whilst great emphasis has been placed on lifestyle factors, a growing body of evidence supports an autoimmune component to atherosclerosis. This study evaluates a novel autoantibody against MYC-associated zinc finger protein (MAZ-Ab) as a potential marker of atherosclerosis. It compares MAZ-Ab to activity on whole-body positron-emission tomography/computed tomography (PET/CT) attributable to atherosclerosis. METHODS: Antibody screening using protein arrays was performed in patients with angiographically-proven ischaemic heart disease. Following MAZ-Ab detection, an ELISA for large-scale testing was developed. An a priori group of unselected patients attending for unrelated 18F-fluorodeoxyglucose (FDG) PET/CT was prospectively enrolled. Each completed a structured questionnaire under supervision and provided serum for analysis. PET/CT scans were evaluated for inflammatory arterial lesions. Whole-body arterial inflammatory burden was then correlated with ELISA optical density for MAZ-Ab. RESULTS: Protein array testing identified IgG anti-MAZ antibodies in 4/6 (67%) patients with ischemic heart disease, versus 0/10 controls. Significant positive correlations between MAZ-Ab and both increasing number of PET positive inflammatory atherosclerostic lesions (p = 0.023) and whole-body arterial inflammatory burden (p = 0.002) were shown. No traditional atherosclerotic risk factor correlated with MAZ-Ab. CONCLUSIONS: A quantitative association between MAZ-Ab optical density on ELISA and the cumulative inflammatory burden of atherosclerosis on 18F-FDG PET/CT could be shown. These findings provide further evidence for an autoimmune component in atherosclerosis and suggest MAZ-Abs as a potential biomarker for atherosclerotic disease.
BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory process of vessel walls responsible for coronary, cerebrovascular and peripheral vascular disease, which together account for the majority of non-infective global deaths. Whilst great emphasis has been placed on lifestyle factors, a growing body of evidence supports an autoimmune component to atherosclerosis. This study evaluates a novel autoantibody against MYC-associated zinc finger protein (MAZ-Ab) as a potential marker of atherosclerosis. It compares MAZ-Ab to activity on whole-body positron-emission tomography/computed tomography (PET/CT) attributable to atherosclerosis. METHODS: Antibody screening using protein arrays was performed in patients with angiographically-proven ischaemic heart disease. Following MAZ-Ab detection, an ELISA for large-scale testing was developed. An a priori group of unselected patients attending for unrelated 18F-fluorodeoxyglucose (FDG) PET/CT was prospectively enrolled. Each completed a structured questionnaire under supervision and provided serum for analysis. PET/CT scans were evaluated for inflammatory arterial lesions. Whole-body arterial inflammatory burden was then correlated with ELISA optical density for MAZ-Ab. RESULTS: Protein array testing identified IgG anti-MAZ antibodies in 4/6 (67%) patients with ischemic heart disease, versus 0/10 controls. Significant positive correlations between MAZ-Ab and both increasing number of PET positive inflammatory atherosclerostic lesions (p = 0.023) and whole-body arterial inflammatory burden (p = 0.002) were shown. No traditional atherosclerotic risk factor correlated with MAZ-Ab. CONCLUSIONS: A quantitative association between MAZ-Ab optical density on ELISA and the cumulative inflammatory burden of atherosclerosis on 18F-FDG PET/CT could be shown. These findings provide further evidence for an autoimmune component in atherosclerosis and suggest MAZ-Abs as a potential biomarker for atherosclerotic disease.
Authors: Diana Ernst; Johan Westerbergh; Georgios Sogkas; Alexandra Jablonka; Gerrit Ahrenstorf; Reinhold Ernst Schmidt; Harald Heidecke; Lars Wallentin; Gabriela Riemekasten; Torsten Witte Journal: Sci Rep Date: 2019-10-10 Impact factor: 4.379
Authors: Diana Ernst; Christian Widera; Niklas T Baerlecken; Wolfgang Schlumberger; Cornelia Daehnrich; Reinhold E Schmidt; Katja Gabrysch; Lars Wallentin; Torsten Witte Journal: Front Immunol Date: 2017-11-21 Impact factor: 7.561