Significance of IFN-γ/IL-2 Ratio as a Circulating Diagnostic Biomarker in Extrapulmonary Tuberculosis

Abstract

Extrapulmonary tuberculosis (EPTB) remains a challenging diagnosis both for clinicians and microbiologists. We hypothesized that the profile of IFN-γ/IL-2 ratio in clinically diagnosed cases of EPTB would be distinct from that of age- and sex-matched healthy controls. Therefore, in our study, we have assessed the ratio of serum levels of IFN-γ and IL-2 in clinically diagnosed cases of EPTB to assess their potential role as diagnostic biomarkers. Sixty-nine (69) clinically confirmed EPTB cases and 69 age- and sex-matched healthy controls were included in the study. All the extrapulmonary specimens were subjected to Ziehl-Neelsen staining for acid-fast bacilli and culture on Lowenstein-Jensen (LJ) medium. Detection of serum levels of IFN-γ and IL-2 was carried out using commercially available ELISA kits following manufacturers' instructions. The ratio of serum levels of IFN-γ and IFN-γ/IL-2 was discriminative for the diagnosis of EPTB cases (p < 0.001), although the same was not observed with IL-2 (p > 0.05). Distribution of all biomarkers significantly differed between culture-positive and culture-negative cases (p < 0.05). Among the smear-positive and smear-negative ones, only IFN-γ and IFN-γ/IL-2 ratio could significantly differentiate (p < 0.05). Ratio of IFN-γ and IL-2 rather than the individual levels was the best discriminatory biomarker with the highest area under the ROC curve. Although IFN-γ and IFN-γ/ IL-2 ratio could aid in the diagnosis of EPTB, IL-2 has a limited utility in the diagnosis of EPTB. Further elaborate studies to validate these results are required.