Endothelial, cytokine, and Th1/cellular host biomarkers discriminate complicated osteoarticular tuberculosis: a prospective single-center cohort study with ROC analysis.

BACKGROUND

Osteoarticular tuberculosis (OATB) accounts for 10-15% of extrapulmonary TB cases and causes progressive bone destruction, neurological compromise, and persistent disability. No validated host-based framework currently identifies patients at high risk of complicated disease course at baseline, and the integrated role of cellular, cytokine, endothelial, and fibrinolytic axes in OATB has not been systematically characterized.

METHODS

We conducted a prospective single-center observational study at Bukhara Regional Center of Phthisiopulmonology, Uzbekistan. Of 223 consecutive eligible adults with confirmed OATB, 115 met immunological-cohort criteria, with peripheral blood drawn before anti-tuberculosis chemotherapy. A priori panel of 20 markers was quantified by flow cytometry and ELISA, covering lymphocyte subpopulations, cytokines, endothelial markers, fibrinolytic markers, and immunoglobulins. Pairwise correlation and ROC analyses with Youden-J thresholding were performed against complicated versus uncomplicated course in 30 prognostic-subset patients.

RESULTS

Nine markers achieved high prognostic discrimination: sICAM-1 (0.89), IL-6 (0.88), sVCAM-1 (0.87), CD4/CD8 (0.86), IP-10 (0.85), TNF-α (0.84), CD95+ (0.83), IFN-γ (0.82), and PAI-1 (0.81), with sensitivities of 76.7-86.7% and specificities of 73.3-83.3%. These markers mapped onto three coupled pathophysiological axes - endothelial-fibrinolytic, pro-inflammatory cytokine, and Th1/cellular with apoptotic priming converging in a plausible immunopathological pattern in complicated disease.

CONCLUSIONS

Nine individually high-performing baseline markers discriminate complicated from uncomplicated OATB with clinically useful accuracy, with endothelial-fibrinolytic markers contributing the highest AUC values. External validation in multi-center cohorts is the essential next step toward routine OATB risk stratification.