Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease

Katharine A. Kott; Adam S. Chan; Stephen T. Vernon; Thomas Hansen; Taiyun Kim; Macha de Dreu; Bavani Gunasegaran; Andrew J. Murphy; Ellis Patrick; Peter J. Psaltis; Stuart M. Grieve; Jean Y. Yang; Barbara Fazekas de St Groth; Helen M. McGuire; Gemma A. Figtree

doi:10.1002/cti2.1462

Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease

Katharine A. Kott, Adam S. Chan, Stephen T. Vernon, Thomas Hansen, Taiyun Kim, Macha de Dreu, Bavani Gunasegaran, Andrew J. Murphy, Ellis Patrick, Peter J. Psaltis, Stuart M. Grieve, Jean Y. Yang, Barbara Fazekas de St Groth, Helen M. McGuire, Gemma A. Figtree

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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 naïve 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.

Original language	English
Article number	e1462
Pages (from-to)	1-18
Number of pages	18
Journal	Clinical and Translational Immunology
Volume	12
Issue number	11
DOIs	https://doi.org/10.1002/cti2.1462
Publication status	Published - 2 Nov 2023
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

atherosclerosis
immune signature
inflammation
mass cytometry
T regulatory cells

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10.1002/cti2.1462Licence: CC BY

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Cite this

Kott, K. A., Chan, A. S., Vernon, S. T., Hansen, T., Kim, T., de Dreu, M., Gunasegaran, B., Murphy, A. J., Patrick, E., Psaltis, P. J., Grieve, S. M., Yang, J. Y., de St Groth, B. F., McGuire, H. M., & Figtree, G. A. (2023). Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease. Clinical and Translational Immunology, 12(11), 1-18. Article e1462. https://doi.org/10.1002/cti2.1462

@article{c9c58ae53d4d4d0693625cef91b58791,

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 = "atherosclerosis, immune signature, inflammation, mass cytometry, T regulatory cells",

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 \{de St Groth\}, \{Barbara Fazekas\} and McGuire, \{Helen M.\} and Figtree, \{Gemma A.\}",

note = "Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2023",

month = nov,

day = "2",

doi = "10.1002/cti2.1462",

language = "English",

volume = "12",

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Kott, KA, Chan, AS, Vernon, ST, Hansen, T, Kim, T, de Dreu, M, Gunasegaran, B, Murphy, AJ, Patrick, E, Psaltis, PJ, Grieve, SM, Yang, JY, de St Groth, BF, McGuire, HM & Figtree, GA 2023, 'Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease', Clinical and Translational Immunology, vol. 12, no. 11, e1462, pp. 1-18. https://doi.org/10.1002/cti2.1462

TY - JOUR

T1 - Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease

AU - Kott, Katharine A.

AU - Chan, Adam S.

AU - Vernon, Stephen T.

AU - Hansen, Thomas

AU - Kim, Taiyun

AU - de Dreu, Macha

AU - Gunasegaran, Bavani

AU - Murphy, Andrew J.

AU - Patrick, Ellis

AU - Psaltis, Peter J.

AU - Grieve, Stuart M.

AU - Yang, Jean Y.

AU - de St Groth, Barbara Fazekas

AU - McGuire, Helen M.

AU - Figtree, Gemma A.

N1 - Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2023/11/2

Y1 - 2023/11/2

N2 - 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 naïve 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.

AB - 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 naïve 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.

KW - atherosclerosis

KW - immune signature

KW - inflammation

KW - mass cytometry

KW - T regulatory cells

UR - https://www.scopus.com/pages/publications/85175866994

U2 - 10.1002/cti2.1462

DO - 10.1002/cti2.1462

M3 - Article

C2 - 37927302

SN - 2050-0068

VL - 12

SP - 1

EP - 18

JO - Clinical and Translational Immunology

JF - Clinical and Translational Immunology

IS - 11

M1 - e1462

ER -

Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease

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