Admission CD4+ T cell BTLA expression and its association with infection risk and respiratory outcomes in sepsis.

OBJECTIVE: T cell co-inhibitory molecule upregulation is linked to sepsis-induced immune suppression, but the relationship between B and T lymphocyte attenuator (BTLA) expression and ICU-acquired infection or organ function recovery in sepsis remains unclear. METHODS: This single-center prospective observational cohort study enrolled 143 septic ICU patients. BTLA on CD4+/CD8+ T cells was measured at ICU admission and on days 3/7. Patients were stratified into high- (n=72) and low- (n=71) BTLA-CD4 groups by median baseline CD4+ BTLA level. Primary outcome was ICU-acquired infection developing more than 48 hours after ICU admission. Secondary outcomes included PaO2/FiO2 ratio, ventilator weaning time, 28-day ventilator-free days and 28-day mortality. RESULTS: The high-expression group had higher ICU-acquired infection (38.9% vs.21.1%, P = 0.033) and 28-day mortality (33.3% vs.9.9%, P = 0.001), but BTLA-CD4 was not an independent predictor for either after multivariable adjustment (infection: OR = 0.937, 95%CI:0.859-1.021, P = 0.139; mortality: HR = 1.034, 95%CI:0.965-1.108, P = 0.342). In a competing-risks analysis accounting for death before weaning, higher BTLA-CD4 was independently associated with delayed ventilator weaning (cause-specific HR = 0.882, 95%CI:0.832-0.936, P<0.001; Fine-Gray subdistribution HR = 0.940, 95%CI:0.902-0.981, P = 0.004). The low-expression group had faster oxygenation recovery and more ventilator-free days (P<0.001). CONCLUSION: Elevated CD4+ T cell BTLA expression at ICU admission is independently associated with delayed ventilator weaning in sepsis. Its links to infection and mortality appear to be driven by disease severity. Admission CD4+ T cell BTLA expression may identify a sepsis immune phenotype associated with impaired respiratory recovery, rather than acting as a direct regulator of lung repair.