AUTHOR=Luo Wei , Sun Jing-Jing , Tang Hao , Fu Di , Hu Zhan-Lan , Zhou Hai-Yang , Luo Wan-Jun , Xu Jun-Mei , Li Hui , Dai Ru-Ping 

TITLE=Association of Apoptosis-Mediated CD4+ T Lymphopenia With Poor Outcome After Type A Aortic Dissection Surgery

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.747467

DOI=10.3389/fcvm.2021.747467

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> Many patients with type A aortic dissection (AAD) show low lymphocyte counts pre-operatively. The present study investigated the prognostic values of lymphopenia and lymphocyte subsets for the postoperative major adverse events (MAEs) in AAD patients undergoing surgery, and explore mechanisms of lymphopenia.</p><p><bold>Methods:</bold> We retrospectively analyzed pre-operative lymphocyte counts in 295 AAD patients treated at two hospitals, and evaluated their correlation with MAEs. We prospectively recruited 40 AAD patients and 20 sex- and age-matched healthy donors (HDs), and evaluated lymphocyte subsets, apoptosis, and pyroptosis by flow cytometry.</p><p><bold>Results:</bold> Multivariable regression analysis of the retrospective cohort revealed pre-operative lymphopenia as a strong predictor of MAEs (odds ratio, 4.152; 95% CI, 2.434–7.081; <italic>p</italic> &lt; 0.001). In the prospective cohort, lymphocyte depletion in the AAD group was mainly due to loss of CD4<sup>+</sup> and CD8<sup>+</sup> T cells as compared with HDs (CD4<sup>+</sup> T cells: 346.7 ± 183.6 vs. 659.0 ± 214.6 cells/μl, <italic>p</italic> &lt; 0.0001; CD8<sup>+</sup> T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/μl, <italic>p</italic> = 0.0036). The apoptosis rates of CD4<sup>+</sup> and CD8<sup>+</sup> T cells were significantly higher in AAD patients relative to HDs (both <italic>p</italic> &lt; 0.0001). Furthermore, the pre-operative CD4<sup>+</sup> T cells count at a cut-off value of 357.96 cells/μl was an effective and reliable predictor of MAEs (area under ROC curve = 0.817; 95% CI, 0.684-0.950; sensitivity, 74%; specificity, 81%; <italic>p</italic> &lt; 0.005). Pre-operative lymphopenia, mainly due to CD4<sup>+</sup> T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery.</p><p><bold>Conclusion:</bold> Pre-operative lymphopenia in particular CD4<sup>+</sup> T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.</p>