PD-1/TIGIT CD4⁺ T-Cell Signature for Risk Stratification of Post-Weaning Mortality in Venoarterial Extracorporeal Membrane Oxygenation Patients.

BACKGROUND

Mortality after successful weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains common, yet few immune biomarkers enable post-weaning risk stratification. We examined whether circulating CD4⁺ T-cell subsets defined by programmed cell death protein 1 (PD-1) and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) were associated with off-ECMO mortality in adults supported with VA-ECMO.

METHODS

We conducted flow cytometric profiling of circulating T cells in 125 adult VA-ECMO patients, classified as survivors (n = 70), on-ECMO mortality (n = 33), and off-ECMO mortality after successful weaning (n = 22). We first quantified CD3⁺, CD4⁺, and CD8⁺ T-cell counts using BD Trucount tubes, and assessed conventional CD4⁺ and CD8⁺ differentiation subsets by flow cytometry. We then quantified PD-1/TIGIT-defined CD4⁺ T cell subsets and assessed their ability to discriminate off-ECMO mortality among successfully weaned patients using receiver operating characteristic (ROC) analyses with bootstrap resampling. A PD-1/TIGIT-based risk classification was constructed using ROC-derived cut-offs.

RESULTS

Although CD3⁺/CD4⁺/CD8⁺ T-cell counts and conventional CD4⁺ differentiation subsets did not differ across outcome groups, the off-ECMO mortality group showed a higher frequency of CD4⁺PD-1-TIGIT⁺ T cells [8.36% (5.65-11.78) vs 5.37% (3.90-7.15), p = 0.005] and a lower frequency of CD4⁺PD-1⁺TIGIT- T cells [10.90% (7.92-14.25) vs 14.95% (10.78-21.85), p = 0.017] compared with survivors. On day 1 of ECMO support, these subsets discriminated off-ECMO mortality with areas under the curve (AUCs) of 0.729 and 0.702, respectively. Based on ROC-derived cut-offs, off-ECMO mortality rates were 10.53%, 16.22%, and 70.59% in the low-, intermediate-, and high-risk groups.

CONCLUSION

A circulating CD4⁺ T cell signature defined by PD-1 and TIGIT expression associates with off-ECMO mortality and may aid risk stratification after VA-ECMO weaning.