@article{cd5541d1cb074f9185ef7fce2ed5c187,
title = "Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease",
abstract = "Objective: The importance of inflammation in atherosclerosis is well accepted, but the role of the adaptive immune system is not yet fully understood. To further explore this, we assessed the circulating immune cell profile of patients with coronary artery disease (CAD) to identify discriminatory features by mass cytometry. Methods: Mass cytometry was performed on patient samples from the BioHEART-CT study, gated to detect 82 distinct cell subsets. CT coronary angiograms were analysed to categorise patients as having CAD (CAD+) or having normal coronary arteries (CAD−). Results: The discovery cohort included 117 patients (mean age 61 ± 12 years, 49% female); 79 patients (68%) were CAD+. Mass cytometry identified changes in 15 T-cell subsets, with higher numbers of proliferating, highly differentiated and cytotoxic cells and decreases in na{\"i}ve T cells. Five T-regulatory subsets were related to an age and gender-independent increase in the odds of CAD incidence when expressing CCR2 (OR 1.12), CCR4 (OR 1.08), CD38 and CD45RO (OR 1.13), HLA-DR (OR 1.06) and Ki67 (OR 1.22). Markers of proliferation and differentiation were also increased within B cells, while plasmacytoid dendritic cells were decreased. This combination of changes was assessed using SVM models in discovery and validation cohorts (area under the curve = 0.74 for both), confirming the robust nature of the immune signature detected. Conclusion: We identified differences within immune subpopulations of CAD+ patients which are indicative of a systemic immune response to coronary atherosclerosis. This immune signature needs further study via incorporation into risk scoring tools for the precision diagnosis of CAD.",
keywords = "T regulatory cells, atherosclerosis, immune signature, inflammation, mass cytometry",
author = "Kott, {Katharine A.} and Chan, {Adam S.} and Vernon, {Stephen T.} and Thomas Hansen and Taiyun Kim and {de Dreu}, Macha and Bavani Gunasegaran and Murphy, {Andrew J.} and Ellis Patrick and Psaltis, {Peter J.} and Grieve, {Stuart M.} and Yang, {Jean Y.} and {Fazekas de St Groth}, Barbara and McGuire, {Helen M.} and Figtree, {Gemma A.}",
note = "Funding Information: We are incredibly grateful to the patients who have donated their imaging results, samples, and time to the BioHEART‐CT study and would like to additionally thank Dr Zara Ali, Dr Luisa Osorio, Meghan Finemore, Christine Yu, Alexander Bate and Michael Gray for operational support of the biobank. We are also most appreciative of the assistance of the radiographers and nursing staff from North Shore Radiology, as well as the pathology staff at Royal North Shore Hospital. We also thank all the support staff at Sydney Cytometry and the Ramaciotti Facility for Human Systems Biology for their assistance with the mass cytometry work. The authors report the following financial support for the research, authorship and/or publication of this article: KAK is supported by an Australian Commonwealth Government Research Training Program Stipend Scholarship; STV is supported by a University of Sydney Postgraduate Research Scholarship funded by Heart Research Australia; HMM is supported by the International Society for the Advancement of Cytometry Marylou Ingram Scholars program. SMG acknowledges the support of the Parker‐Hughes Bequest, the New South Wales Office of Health and Medical Research, and the Frecker Family; GAF is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT11359290), the Medical Research Future Fund (Australia), Heart Research Australia, the New South Wales Office of Health and Medical Research, and NSW Pathology (NSW Statewide Biobank). Funding Information: We are incredibly grateful to the patients who have donated their imaging results, samples, and time to the BioHEART-CT study and would like to additionally thank Dr Zara Ali, Dr Luisa Osorio, Meghan Finemore, Christine Yu, Alexander Bate and Michael Gray for operational support of the biobank. We are also most appreciative of the assistance of the radiographers and nursing staff from North Shore Radiology, as well as the pathology staff at Royal North Shore Hospital. We also thank all the support staff at Sydney Cytometry and the Ramaciotti Facility for Human Systems Biology for their assistance with the mass cytometry work. The authors report the following financial support for the research, authorship and/or publication of this article: KAK is supported by an Australian Commonwealth Government Research Training Program Stipend Scholarship; STV is supported by a University of Sydney Postgraduate Research Scholarship funded by Heart Research Australia; HMM is supported by the International Society for the Advancement of Cytometry Marylou Ingram Scholars program. SMG acknowledges the support of the Parker-Hughes Bequest, the New South Wales Office of Health and Medical Research, and the Frecker Family; GAF is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT11359290), the Medical Research Future Fund (Australia), Heart Research Australia, the New South Wales Office of Health and Medical Research, and NSW Pathology (NSW Statewide Biobank). Publisher Copyright: {\textcopyright} 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.",
year = "2023",
month = nov,
day = "2",
doi = "10.1002/cti2.1462",
language = "English",
volume = "12",
journal = "Clinical and Translational Immunology",
issn = "2050-0068",
publisher = "John Wiley & Sons Inc.",
number = "11",
}