Messenger RNA Expression of IL-8, FOXP3, and IL-12β Differentiates Latent Tuberculosis Infection from Disease

Abstract

Differentiation of active from latent tuberculosis (TB) is a major challenge in the control of TB. In this study, PBMC from latent TB-infected subjects, TB patients, and tuberculin skin test-negative donors stimulated with the Mycobacterium tuberculosis (Mtb)-specific Ag, early secretory antigenic target 6, and mRNA for 45 immune-related genes was measured by quantitative real-time PCR. Univariate analysis showed significant differences in the expression of 10 genes (IFN-γ, FOXP3, IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-12α, IL-12β, and IL-24) in PBMC from TB patients vs latent TB-infected subjects (p < 0.01). Multivariate logistic regression and classification and regression tree analyses revealed that expression of three genes, IL-8, FOXP3, and IL-12β, is predictive for TB vs latent Mtb infection. Thus, measurement of Ag-specific expression of these three genes may offer a specific and noninvasive means of differentiating between latent Mtb infection and TB.

Frequencies of Region of Difference 1 Antigen-Specific but Not Purified Protein Derivative-Specific Gamma Interferon-Secreting T Cells Correlate with the Presence of Tuberculosis Disease but Do Not Distinguish Recent from Remote Latent Infections

“…For example, the shift from dominance of T cells secreting only IFN-␥ toward codominance of antigen-specific CD4 ϩ T cells secreting IL-2 and IL-2 plus IFN-␥-during treatment of active disease (29) suggests that a dual cytokine signature may correlate better with antigen load than measurement of only one cytokine. Indeed, one recent study suggested that simultaneous measurement of transcription of six cytokines by real-time reverse transcription-PCR may distinguish between active TB infection and LTBI, although the study sample size was small (42). Given that RD1-specific IFN-␥-secreting T cells correlate better with pathology than with protective immunity, measuring cytokine secretion profiles of RD1 antigen-specific T cells may in the future enable accurate discrimination of active infection from latent infection.…”

Diverse Pattern of Cytokine Production, their Functional Association and mRNA Expression in Tuberculosis Patients with Diabetes Mellitus and their Household Contacts

“…In this study, PTB patients and PTB HHC have not shown any significant difference during their follow up. IL-1β expression up-regulated in the alveolar macrophages of TB patients in a Chinese study and was significantly low in ESAT-6 stimulated PBMC of PTB patients when compared to the LTBI individuals, however statistical significance was not observed with respect to healthy controls [32,33]. IL-1β expression was low in the DM compared to HCs, which was contrary to a study where increased IL-1β mRNA was examined in the beta cells of DM patients with minimal or no expression [34].…”

Advances in tuberculosis

“…A recent meta-analysis suggested that IGRAs do not have high predictive value for development of active tuberculosis ( (Rangaka et al, 2011) and concluded that the identification of better predictive markers was essential. Promising results have been reported in this regard with the use of poly-cytokine bio-signatures (Chegou et al, 2009) and measurement of expression levels of mRNA transcripts for IL-8, FOXp3 and IL-12  in ESAT-6 stimulated polymorphonuclear cells (Wu et al, 2007). T cells secreting only TNF have recently been proposed as indicators for active TB (Harari et al, 2011).…”