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

BACKGROUND AND AIMS

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 and CD8 T cells in patients with ADHF and its impact on their prognosis.

METHODS

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 and CD8 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.

RESULTS

We found that the Tim-3 expression on CD4 T cells [2.08% (1.15-2.67%) vs. 0.88% (0.56-1.39%), < 0.001] and CD8 T cells [3.81% (2.24-6.03%) vs. 1.36% (0.76-3.00%), < 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 and CD8 T cells were independent risk factors of ADHF (OR: 2.76; 95% CI: 1.34-5.65, = 0.006; OR: 2.58; 95% CI: 1.26-5.31, = 0.010, respectively). ROC curve analysis showed that the high level of Tim-3 on CD4 or CD8 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 and CD8 T cells were strongly associated with increased risks of MACCE within 12 months after ADHF (HR: 2.613; 95% CI: 1.11-6.13, = 0.027; HR: 2.762, 95% CI: 1.15-6.63, = 0.023; respectively).

CONCLUSION

Our research indicated that the expression level of Tim-3 on CD4 and CD8 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.