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. 2024 Dec 6;135(12):1193-1195.
doi: 10.1161/CIRCRESAHA.124.325183. Epub 2024 Oct 21.

Cytotoxic T Cells Drive Outcome in Inflammatory Dilated Cardiomyopathy

Maurits A Sikking  1 , Daniel Harding  2   3 , Michiel T H M Henkens  1   4   5 , Sophie L V M Stroeks  1   6   7   8 , Max F G H M Venner  1 , Bastien Nihant  1 , Rick E W van Leeuwen  1 , Silvia Fanti  2 , Xiaofei Li  4 , Pieter van Paassen  9 , Christian Knackstedt  1 , Hans-Peter Brunner-la Rocca  1 , Vanessa P M van Empel  1 , Job A J Verdonschot  1   6   7 , Federica M Marelli-Berg #  2   10   3 , Stephane R B Heymans #  1   7   8
Affiliations

Cytotoxic T Cells Drive Outcome in Inflammatory Dilated Cardiomyopathy

Maurits A Sikking et al. Circ Res. .
No abstract available

Keywords: allergy and immunology; cardiomyopathy, dilated; heart failure; leukocytes, mononuclear; myocarditis.

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Conflict of interest statement

S.R.B. Heymans receives fees for scientific advice for AstraZeneca, Ribocure, and CSL Behring and receives research support from AstraZeneca and CSL Behring. The other authors report no conflicts.

Figures

Figure.
Figure.
Circulating and cardiac cytotoxic T cells (Tc cells) drive poor outcomes in inflammatory dilated cardiomyopathy. A, Clinical characteristics comparison between non-inflammatory DCM (non-infl-DCM) and inflammatory DCM (infl-DCM) shows no between-group differences. However, cardiac T cells and Tc cells and macrophages are increased in infl-DCM compared with non-infl-DCM (P=6.2×10−10, P=9.4×10−10, and P=4.2×10−5, respectively). Genetic mutations were found in TTN, FLNC, and MYBPC3 in infl-DCM and MYH7 in non-infl-DCM. B, The proportion of circulating Tc cells in infl-DCM was increased compared with non-infl-DCM (P=0.04). C, In the total study cohort (n=125), the proportion of circulating Tc cells correlated with the density of Tc cells in endomyocardial biopsy (EMB; Spearmanρ=0.43; P=3.8×10−4). D, An example of Tc cell staining of an EMB of infl-DCM. E, Comparison of cardiac gene expression by transcriptomics of EMBs of non-infl-DCM and infl-DCM patients shows higher expression of PRF1 (perforin-1), GZMA (granzyme-A), GZMH (granzyme-H), and IL17RC (interleukin-17 receptor-C), after correcting for multiple testing (false discovery rate [FDR] <0.1 as per Benjamini-Hochberg procedure). Expression of these genes was not associated with prognosis. F, In the total study cohort (n=125), high cardiac Tc cells (≥3 Tc cells/mm2 corresponding with the third quartile of cardiac Tc cells) correlated with a worse prognosis compared with low cardiac Tc cells (<3 Tc cells/mm2) as tested by log-rank test (P=0.04). *Fisher exact or Mann-Whitney U test; **Mann-Whitney U test; and ***2-sample t tests. a. fib indicates atrial fibrillation; CD, cluster of differentiation; GZMB, granzyme-B; IL17RA, interleukin-17 receptor-A; IL-6, interleukin-6; LGE, late-gadolinium enhancement; LVEF, left ventricle ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association dyspnea classification; T1/T2, T1- or T2-weighted imaging; and TGFB1, tumor growth factor-β1.
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