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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article numbere1462
Pages (from-to)1-18
Number of pages18
JournalClinical and Translational Immunology
Volume12
Issue number11
DOIs
Publication statusPublished - 2 Nov 2023
Externally publishedYes

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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