The Balance of CD8-Positive T Cells and PD-L1 Expression in the Myocardium Predicts Prognosis in Lymphocytic Fulminant Myocarditis

Abstract

Introduction

The clinical significance and prognostic value of T cell involvement and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) have not been established in lymphocytic fulminant myocarditis (FM). We investigated the prognostic impact of the number of CD4 ⁺, CD8 ⁺, FoxP3 ⁺, and PD-1 ⁺ T cells, as well as PD-L1 expression, in cardiomyocytes in lymphocytic FM.

Methods

This is a single-center observational cohort study. Myocardial tissue was obtained from 16 consecutive patients at lymphocytic FM onset. The median follow-up was 140 days. Cardiac events were defined as a composite of cardiac death and left ventricular-assist device implantation. CD4, CD8, FoxP3, PD-1, and PD-L1 immunostaining were performed on myocardial specimens.

Results

The median age of the patients was 52 years (seven men and nine women). There was no significant difference in the number of CD4 ⁺ cells. The number of CD8 ⁺ cells and the CD8 ⁺/CD4 ⁺ T cell ratio were higher in the cardiac event group (Event+) than in the group without cardiac events (Event−) ( p = 0.048 and p = 0.022, respectively). The number of FoxP3 ⁺ T cells was higher in the Event+ group ( p = 0.049). Although there was no difference in the number of PD-1 ⁺ cells, cardiomyocyte PD-L1 expression was higher in the Event+ group ( p = 0.112). Event-free survival was worse in the group with a high CD8 ⁺ cell count ( p = 0.012) and high PD-L1 expression ( p = 0.049). When divided into three groups based on the number of CD8 ⁺ cells and PD-L1 expression (CD8 ^highPD-L1 ^high [ n = 8], CD8 ^lowPD-L1 ^high [ n = 1], and CD8 ^lowPD-L1 ^low [ n = 7]), the CD8 ^highPD-L1 ^high group demonstrated the worst event-free survival, while the CD8 ^lowPD-L1 ^high group had a favorable prognosis without cardiac events ( p = 0.041).

Conclusion

High myocardial expression of CD8 ⁺ T cells and PD-L1 may predict a poor prognosis in lymphocytic FM.

Plain Language Summary

Myocarditis is a heart condition caused by inflammation of the heart muscle. Fulminant myocarditis (FM) is a severe form that can lead to sudden heart failure, shock, or dangerous heart rhythms. Understanding how the immune system is involved in FM is crucial for finding better treatments. In this study, we examined heart tissue from 16 patients with lymphocytic FM to understand the role of specific immune cells (T cells) and molecules (PD-1 and PD-L1) in the disease. We followed the patients for about 5 months to track their outcomes. We found that patients with more CD8+ T cells (a type of immune cell) in their heart tissue had a higher risk of cardiac events such as heart failure. Furthermore, when a specific molecule called PD-L1 was more abundant in heart cells, it indicated a poorer prognosis. This suggests that high levels of CD8+ T cells and PD-L1 in the heart tissue can predict a worse outcome for patients with lymphocytic FM. Understanding these markers may help doctors identify patients at higher risk and tailor treatments to improve their prognosis. However, more research with larger groups of patients is needed to confirm these findings and guide treatment decisions.