Monitoring T-cell function in septic shock: one-year experience with a fully automated assay

In sepsis, personalized immunotherapy is being evaluated as a strategy to restore immune function in the most severely affected patients. Biomarkers are critical in this process, as clear clinical indicators of immune status are lacking. Functional testing is considered the gold standard for assessing immune function, but its clinical implementation faces analytical and standardization challenges. The objective of the present prospective, observational, single-center cohort study was to evaluate a fully automated protocol for assessing T cell functionality in septic shock patients. In 66 patients with septic shock, we assessed T lymphocyte functionality using an interferon-γ release assay (IGRA) in response to mitogen. The assay was performed via a fully automated protocol during a one-year period. Patients were monitored three times during the first week after intensive care unit (ICU) admission. Phenotypic immunological parameters, including T cell subpopulation counts and monocyte HLA-DR expression (mHLA-DR), were also assessed. Patient outcomes were followed for 28 days, and a composite clinical deterioration score was defined by the occurrence of 28-day mortality and/or ICU-acquired infection. Compared with reference values, we observed a significant reduction in IFN-γ release capacity, which correlated with characteristic alterations in cellular immunological parameters. By the end of the first week, reduced IFN-γ release combined with low mHLA-DR identified a severe immunological phenotype associated with an increased risk of clinical deterioration. Given the observational nature of this study, further well-designed investigations in larger patient cohorts are required to validate these findings and assess their potential clinical relevance. If confirmed, this fully automated assay (performed on whole blood, requiring no technician intervention, and providing results within four hours) may offer a practical tool for monitoring immune functional alterations in routine clinical practice.