AUTHOR=Meng Xin , Xia Guofang , Zhang Lili , Xu Congfeng , Chen Zhong 

TITLE=T cell immunoglobulin and mucin domain-containing protein 3 is highly expressed in patients with acute decompensated heart failure and predicts mid-term prognosis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.933532

DOI=10.3389/fcvm.2022.933532

ISSN=2297-055X

ABSTRACT=<sec><title>Background and aims</title><p>T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is mainly expressed by immune cells and plays an immunomodulatory role in cardiovascular disease. However, the prognostic value of Tim-3 in acute decompensated heart failure (ADHF) is unclear. This study aimed to investigate the expression profile of Tim-3 on CD4<sup>+</sup> and CD8<sup>+</sup> T cells in patients with ADHF and its impact on their prognosis.</p></sec><sec><title>Methods</title><p>In this prospective study, 84 patients who were hospitalized with ADHF and 83 patients without heart failure were enrolled. Main clinical data were collected during patient visits. The Tim-3 expression on CD4<sup>+</sup> and CD8<sup>+</sup> T cells in peripheral blood samples was assayed by flow cytometry. Long-term prognosis of the patients with ADHF was evaluated by major adverse cardiac and cerebrovascular events (MACCE) over a 12-month follow-up period.</p></sec><sec><title>Results</title><p>We found that the Tim-3 expression on CD4<sup>+</sup> T cells [2.08% (1.15–2.67%) vs. 0.88% (0.56–1.39%), <italic>p</italic> &lt; 0.001] and CD8<sup>+</sup> T cells [3.81% (2.24–6.03%) vs. 1.36% (0.76–3.00%), <italic>p</italic> &lt; 0.001] in ADHF group were significantly increased vs. the non-ADHF group. Logistic analysis revealed that high levels of Tim-3 expressed on CD4<sup>+</sup> and CD8<sup>+</sup> T cells were independent risk factors of ADHF (OR: 2.76; 95% CI: 1.34–5.65, <italic>p</italic> = 0.006; OR: 2.58; 95% CI: 1.26–5.31, <italic>p</italic> = 0.010, respectively). ROC curve analysis showed that the high level of Tim-3 on CD4<sup>+</sup> or CD8<sup>+</sup> T cells as a biomarker has predictive performance for ADHF (AUC: 0.75; 95% CI: 0.68–0.83; AUC: 0.78, 95% CI: 0.71–0.85, respectively). During a median follow-up of 12 months, the Cox regression analysis revealed that higher Tim-3 on CD4<sup>+</sup> and CD8<sup>+</sup> T cells were strongly associated with increased risks of MACCE within 12 months after ADHF (HR: 2.613; 95% CI: 1.11–6.13, <italic>p</italic> = 0.027; HR: 2.762, 95% CI: 1.15–6.63, <italic>p</italic> = 0.023; respectively).</p></sec><sec><title>Conclusion</title><p>Our research indicated that the expression level of Tim-3 on CD4<sup>+</sup> and CD8<sup>+</sup> T cells, elevated in patients with ADHF, was an independent predictor of MACCE within 12 months after ADHF. It suggests a potential immunoregulatory role of Tim-3 signaling system in the mechanism of ADHF.</p></sec>