The primary goals of this study are to compare the differences in tissue-resident Treg gene signature for activation, proliferation, and suppressive function using single-cell/-nucleus RNA sequencing in patients treated with ld-IL-2 compared to control grouped by individual tissue beds from in and around the heart. Additionally, tissue-resident Tregs will be compared to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2 on the two compartments.
Aged over 18 years old
Undergoing CABG surgery
Critical left main stem coronary disease
Severe valvular disease (for example 'severe' aortic stenosis as classified on echocardiogram report)
Haemodynamic instability caused by arrhythmia requiring cardioversion in the current admission
Non-sustained ventricular tachycardia of >10 beats in the last 48 hours
Parallel
Interleukin-2 (Aldesleukin)
Drug5 sequential days of treatment (1.5MIU/day subcutaneously) and, if needed, 1.5MIU/week doses until CABG surgery completed
Standard care
Procedure/SurgeryStandard care for patients with coronary artery disease undergoing CABG surgery
Interleukin-2 (Aldesleukin)
Drug5 sequential days of treatment (2.0MIU/day subcutaneously) and, if needed, 2.0MIU/week doses until CABG surgery completed
Compare the differences in tissue-resident Treg gene signature in patients treated with ld-IL-2 compared to control
Assessing Tregs from the various tissue beds and comparing differential gene expression markers for tissue healing and inflammation using sc/snRNA-sequencing technologies
Comparing tissue-resident Tregs to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2
Comparing the tissue Tregs against blood Tregs from the same patient by comparing differential gene expression markers for tissue healing and inflammation using sc/snRNA-sequencing technologies and looking for differences between the two compartments.
Difference in inflammatory T effector cells
Comparing differential gene expression using sc/snRNA-sequencing technologies from isolated effector T cells between the 3 patient groups (control, 1.5MIU and 2.0MIU)
Difference in other immune cells
Comparing differential gene expression using sc/snRNA-sequencing technologies from other immune cells (e.g. B cells) between the 3 patient groups (control, 1.5MIU and 2.0MIU)
Comparing T cell receptor repertoire
Comparing differences in T cell receptor (TCR) repertoire using TCR sequencing technologies between the 3 patient groups (control, 1.5MIU and 2.0MIU)
Comparing tissue-resident immune cells to circulating immune cells
Tissue-resident immune cells will be compared to peripheral/circulating immune cells from the same patient using sc/snRNA-seq technologies to compare the differential effect of ld-IL-2 on the two compartments.
Systemc biomarkers of inflammation and tissue damage
Compare blood-based inflammation markers and assays between the three patient groups (control, 1.5MIU, 2.0MIU)
Non-immune cells and cardiomyocytes
Compare stromal and myocardial cells on sc/snRNA-seq technologies between the three patient groups (control, 1.5MIU, 2.0MIU)
Characterise tissue-level gene signatures
Tissue-level RNA expression will be evaluated on sc/snRNA-sequencing technologies
Gut microbiota
Compare stool-based analysis of microbiota between the three patient groups (control, 1.5MIU, 2.0MIU)
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Cambridge University Hospitals NHS Foundation Trust
Lead sponsor
Royal Papworth Hospital
Collaborator
