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

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. 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. 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; < 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, < 0.0001; CD8 T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/μl, = 0.0036). The apoptosis rates of CD4 and CD8 T cells were significantly higher in AAD patients relative to HDs (both < 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%; < 0.005). Pre-operative lymphopenia, mainly due to CD4 T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery. Pre-operative lymphopenia in particular CD4 T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.