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

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

doi:10.3389/fcvm.2021.747467

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

Front Cardiovasc Med. 2021 Nov 12:8:747467. doi: 10.3389/fcvm.2021.747467. eCollection 2021.

Authors

Wei Luo¹, Jing-Jing Sun¹, Hao Tang², Di Fu³, Zhan-Lan Hu¹, Hai-Yang Zhou¹, Wan-Jun Luo⁴, Jun-Mei Xu¹, Hui Li¹, Ru-Ping Dai¹

Affiliations

¹ Department of Anesthesiology, The Second XiangYa Hospital, Central South University, Changsha, China.
² Department of Cardiovascular Surgery, The Second XiangYa Hospital, Central South University, Changsha, China.
³ Department of Anesthesiology, XiangYa Hospital, Central South University, Changsha, China.
⁴ Department of Cardiovascular Surgery, XiangYa Hospital, Central South University, Changsha, China.

Abstract

Background: 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. Methods: 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. Results: 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; p < 0.001). In the prospective cohort, lymphocyte depletion in the AAD group was mainly due to loss of CD4⁺ and CD8⁺ T cells as compared with HDs (CD4⁺ T cells: 346.7 ± 183.6 vs. 659.0 ± 214.6 cells/μl, p < 0.0001; CD8⁺ T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/μl, p = 0.0036). The apoptosis rates of CD4⁺ and CD8⁺ T cells were significantly higher in AAD patients relative to HDs (both p < 0.0001). Furthermore, the pre-operative CD4⁺ 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%; p < 0.005). Pre-operative lymphopenia, mainly due to CD4⁺ T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery. Conclusion: Pre-operative lymphopenia in particular CD4⁺ T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.

Keywords: CD4+ T lymphopenia; aortic dissection; apoptosis; major adverse events; outcomes.