Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis

Objectives: To evaluate cytokine profiles and interferon -gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non -TB conditions, as well as smear -negative pulmonary tuberculosis (SNPT) from smear -positive pulmonary tuberculosis (SPPT). Methods: A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). Results: Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP ( p <0.05). TB patients showed higher IL-2, IL-6, IFN- gamma , IL-8 ( p <0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p <0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN- alpha , IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p =0.015). ROC analysis indicated IFN- alpha , IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). Conclusion: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.