TNF-α and IFN-γ Cytokine Profiles Distinguish Pulmonary From Extrapulmonary Tuberculosis: A Diagnostic Accuracy Study

Background: Tuberculosis (TB) remains a global health challenge, with pulmonary (PTB) and extrapulmonary (EPTB) forms requiring different diagnostic approaches. Cytokine profiles, particularly tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), may serve as potential biomarkers for distinguishing between TB manifestations. Objectives: To determine whether TNF-α and IFN-γ cytokine levels and their ratio can distinguish between PTB and EPTB patients compared to healthy controls, and to evaluate their diagnostic performance as biomarkers. Materials and Methods: This cross-sectional study enrolled 200 participants from Baghdad, Iraq, including 80 PTB patients, 60 EPTB patients, and 60 healthy controls. Serum TNF-α and IFN-γ levels were measured using enzyme-linked immunosorbent assay (ELISA). The TNF-α/IFN-γ ratio was calculated, and diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: PTB patients demonstrated significantly higher IFN-γ levels (229.07 ± 45.3 pg/mL) compared to EPTB patients (90.14 ± 21.8 pg/mL) (p<0.001). TNF-α levels were comparable between PTB (105.22 ± 18.6 pg/mL) and EPTB (106.62 ± 19.2 pg/mL) groups. The TNF-α/IFN-γ ratio was significantly higher in PTB (2.395 ± 0.84) versus EPTB (2.134 ± 0.76) patients. Among EPTB subtypes, lymph node TB was most prevalent (51.7%), followed by genitourinary (18.3%) and skin TB (13.3%). The TNF-α/IFN-γ ratio showed 78% sensitivity and 72% specificity for differentiating PTB from EPTB at a cut-off value of 2.25. Conclusion: Cytokine profiling, particularly IFN-γ levels and the TNF-α/IFN-γ ratio, demonstrates promising diagnostic potential for distinguishing PTB from EPTB. These biomarkers could complement existing diagnostic tools, potentially improving TB diagnosis and management strategies.