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 discrimin...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Clinical & Translational Immunology |
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| Online Access: | https://doi.org/10.1002/cti2.1462 |
| _version_ | 1797450873880707072 |
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| author | Katharine A Kott Adam S Chan Stephen T Vernon Thomas Hansen Taiyun Kim Macha deDreu 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 |
| author_facet | Katharine A Kott Adam S Chan Stephen T Vernon Thomas Hansen Taiyun Kim Macha deDreu 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 |
| author_sort | Katharine A Kott |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T14:46:48Z |
| format | Article |
| id | doaj.art-c6896394e4c5467bb8255df0f5093c80 |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-03-09T14:46:48Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-c6896394e4c5467bb8255df0f5093c802023-11-27T04:26:39ZengWileyClinical & Translational Immunology2050-00682023-01-011211n/an/a10.1002/cti2.1462Mass cytometry analysis reveals altered immune profiles in patients with coronary artery diseaseKatharine A Kott0Adam S Chan1Stephen T Vernon2Thomas Hansen3Taiyun Kim4Macha deDreu5Bavani Gunasegaran6Andrew J Murphy7Ellis Patrick8Peter J Psaltis9Stuart M Grieve10Jean Y Yang11Barbara Fazekas de St Groth12Helen M McGuire13Gemma A Figtree14Cardiothoracic and Vascular Health Kolling Institute of Medical Research Sydney NSW AustraliaSchool of Mathematics and Statistics University of Sydney Sydney NSW AustraliaCardiothoracic and Vascular Health Kolling Institute of Medical Research Sydney NSW AustraliaCardiothoracic and Vascular Health Kolling Institute of Medical Research Sydney NSW AustraliaSchool of Mathematics and Statistics University of Sydney Sydney NSW AustraliaSchool of Medical Sciences, Faculty of Medicine and Health University of Sydney Sydney NSW AustraliaCharles Perkins Centre University of Sydney Sydney NSW AustraliaBaker Heart and Diabetes Institute Melbourne VIC AustraliaSchool of Mathematics and Statistics University of Sydney Sydney NSW AustraliaMonash Cardiovascular Research Centre Clayton VIC AustraliaCharles Perkins Centre University of Sydney Sydney NSW AustraliaSchool of Mathematics and Statistics University of Sydney Sydney NSW AustraliaCharles Perkins Centre University of Sydney Sydney NSW AustraliaCharles Perkins Centre University of Sydney Sydney NSW AustraliaCardiothoracic and Vascular Health Kolling Institute of Medical Research Sydney NSW AustraliaAbstract 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.https://doi.org/10.1002/cti2.1462atherosclerosisimmune signatureinflammationmass cytometryT regulatory cells |
| spellingShingle | Katharine A Kott Adam S Chan Stephen T Vernon Thomas Hansen Taiyun Kim Macha deDreu 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 Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease Clinical & Translational Immunology atherosclerosis immune signature inflammation mass cytometry T regulatory cells |
| title | Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease |
| title_full | Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease |
| title_fullStr | Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease |
| title_full_unstemmed | Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease |
| title_short | Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease |
| title_sort | mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease |
| topic | atherosclerosis immune signature inflammation mass cytometry T regulatory cells |
| url | https://doi.org/10.1002/cti2.1462 |
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