TREC dynamics as a biomarker of naive T-cell homeostasis in traumatic brain injury: a longitudinal analysis

Post-traumatic immunosuppression complicates recovery from traumatic brain injury (TBI), increasing susceptibility to infection. Reliable biomarkers to assess immune status are required. We investigated the dynamics of T-cell receptor excision circles (TREC) and B-cell K-deleting recombination excision circles (KREC) as potential markers of immune homeostasis in TBI patients. In this observational study, 51 patients with moderate-to-severe TBI were enrolled. Serial peripheral blood samples were collected for the purpose of quantifying TREC and KREC levels using real-time PCR. Linear mixed-effects models (LMMs) were employed to analyze the longitudinal dynamics and identify clinical predictors. Principal Component Analysis (PCA) was applied to construct a composite severity/inflammation index, and the final model was validated using a cluster bootstrap procedure. In most patients, the baseline TREC level was close to or below the lower age-matched norms. TREC and KREC levels fluctuated greatly, with non-monotonic changes and multi-fold variations. Three patients with decreasing TREC dynamics subsequently succumbed to sepsis. Lower TREC levels were robustly associated with older age and a higher severity/inflammation index (p < 0.001), while KREC dynamics remained independent of the examined clinical and inflammatory parameters. TREC levels restoration was synchronous with neurological improvement (rising GCS) and the resolution of organ dysfunction (declining SOFA). By offering a window into a key, potentially modifiable biological mechanism underlying patient vulnerability, TREC analysis represents a promising new approach for risk stratification and the development of future immunotherapeutic strategies in neurocritical care.