CTLA-4 and CD154 expression on peripheral T cells as diagnostic biomarkers for pulmonary tuberculosis

Current tuberculosis (TB) diagnostics are often sputum-dependent with suboptimal performance. There is a critical need to develop blood-based host biomarkers for rapid diagnosis.

A total of 173 adults (99 pulmonary TB, 74 non-TB respiratory controls) were enrolled. Flow cytometry measured T-cell surface markers (CTLA-4, CD154, GITR, ICOS) on CD4⁺ and CD8⁺ subsets. Clinical variables such as C-reactive protein (CRP), body mass index (BMI) were recorded. Univariate/multivariate analyses and a random forest model were used to identify TB predictors and assess diagnostic performance via receiver operating characteristic (ROC) analysis.

CTLA-4⁺CD4⁺, CTLA-4⁺CD8⁺, and CD154⁺CD4⁺ T-cells were significantly lower in TB patients (P < 0.05). Elevated CRP and low BMI were independent predictors. Individual markers showed moderate accuracy (Area under curve (AUC) 0.57-0.65), but a model combining CTLA-4 and CD154 achieved excellent discrimination (AUC, 0.897). Adding CRP and BMI further improved performance (AUC, 0.930).

An integrated blood signature combining CTLA-4, CD154, CRP, and BMI effectively discriminates pulmonary TB from other respiratory diseases, offering a rapid, non-sputum adjunctive diagnostic tool.