QuantiFERON-TB Gold Plus Assay in Patients With Latent vs. Active Tuberculosis in a Low Incidence Setting: Level of IFN-γ, CD4/CD8 Responses, and Release of IL-2, IP-10, and MIG

Abstract

ObjectivesWe analyzed the results of the QuantiFERON Glod Plus assay (QFT) and cytokine patterns associated with active tuberculosis (ATB) among patients with positive QFT.MethodsA total of 195 patients are QFT-positive, among which 24 had an ATB and 171 had a latent tuberculosis infection (LTBI). Interferon-gamma (IFN-γ) secretion was analyzed relative to interleukin-2 (IL-2), IFN-γ inducible protein or CXCL-10 (IP-10), and monokine induced by IFN-γ or CXCL-9 (MIG) secretion, and then compared between two sets of peptide antigens [tube 1 - cluster of differentiation 4 (CD4+) T cell stimulation; tube 2 - CD4+/CD8+ T cell response].ResultsHigher IFN-γ responses were measured in the ATB group (p = 0.0089). The results showed that there was a lower ratio of tube 1/tube 2 IFN-γ concentrations in the ATB group (p = 0.0009), and a median [interquartile ranges (IQR)] difference between the two sets at −0.82 IU/ml (−1.67 to 0.18) vs. −0.07 IU/ml (−0.035 to 0.11, p < 0.0001) in the ATB group compared to the LTBI group, respectively. In addition, patients with low ratios of IL-2/IFN-γ, IP-10/IFN-γ, and MIG/IFN-γ were much more likely to have ATB.ConclusionHigh levels of IFN-γ secretion, preferential IFN-γ response in tube 2, and lower secretion of IL-2, IP-10, and MIG release relative to IFN-γ secretion were more likely observed in subjects with ATB. These features of T cell response may be helpful in low prevalence settings to suspect ATB in patients tested positive for IFN-γ release assays (IGRA).

The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection

“…Another series of chemokines, including CXCL9 , CXCL10 , and CXCL18 , are highly expressed in TB. Our study and other previous studies used CXCL10 and CXCL9 to diagnose active TB [ 19 , 20 ]. We evaluated the extent to which the immunoregulatory features identified in BALF manifested in the peripheral blood.…”

Association of Cytokine Gene Polymorphisms and Their Impact on Active and Latent Tuberculosis in Brazil’s Amazon Region

“…Thus, genetic variations in these cytokine genes may promote susceptibility to active infection and the establishment of TB symptom manifestations. These results reinforce that the immune responses generated against Mtb need to be adequately balanced to eliminate or promote the latency state of the bacillus [51,56,57]. Approximately 5 to 10% of individuals with LTBI progress to active infection during their lifetime [5].…”

Re-evaluating the Role of Antibodies in Tuberculosis

“…IFNlevels during active TB disease and levels after cure of clinical TB disease were not significantly different (Petruccioli et al, 2017). Although a significant difference between LTBI and active TB was found, responses were overlapping between groups making the use of IGRA to distinguish between active and LTBI unfeasible (Carrère-Kremer et al, 2022;Petruccioli et al, 2017).…”