TB Antigen-Stimulated CXCR3 Ligand Assay for Diagnosis of Tuberculous Lymphadenitis

Abstract

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.

Improving interferon-γ release assay interpretation: are IP-10 and MIG the solution?

“…IP-10 and MIG are both recognised actors of the host's defence against an infection sustained by MTB and target of several studies that over the years have tried to use these biomarkers for TB diagnosis [17]. In particular, an involvement of IP-10 and MIG has been reported in the immunity cascade linked to granuloma formation [18,19], as well as an increase in the serum levels of IP-10 and MIG during TB infection [20]. MIG and IP-10 level decrease has also been associated with response to TB therapy [21] and lateral flow assays employing IP-10 as readout marker are currently under development, even if little information is available on their performance [2].…”