Diagnostic accuracy of combinations of serological biomarkers for identifying clinical tuberculosis.

INTRODUCTION: Confirmation of tuberculosis (TB) cases in endemic TB settings is a challenge; obtaining fast and cheap, though accurate, diagnostic tools such as biomarkers is thus urgently needed to enable the early detection of TB. This paper evaluates the diagnostic accuracy of combinations of host serological biomarkers for identifying TB. METHODOLOGY: Enzyme-linked immunosorbent assays (ELISA) were used on 70 Venezuelan Creole individuals for evaluating host biomarkers (i.e. CXCL9, sCD14, MMP9 and uPAR proteins) and anti-synthetic peptides covering certain Mycobacterium tuberculosis (Mtb) ESAT-6 (P-12033, P-12034 and P-12037) and Ag85A (P-29878) antigen sequences. The target population consisted of adults having active TB (ATB, n = 28), the tuberculin skin test positive (TST+) or individuals with latent TB infection (LTB, n = 28) and TST- or control subjects (CTRL, n = 14). RESULTS: Receiver operator curve (ROC) analysis revealed good biosignature discriminative ability for 5 serological biomarkers; the accuracy of 3 combinations had a good discriminative ability for diagnosing TB. Anti-P-12034/uPAR detected TB with 96.7% sensitivity and 86.0% specificity, followed by anti-P-12033/uPAR having 96.7% sensitivity and 81.4% specificity. Anti-P-29878/MMP9 had the highest sensitivity (100%), but low specificity (52.17%). Biomarker combinations did not prove efficacious for identifying incipient subclinical TST+TB- subjects at high-risk for TB. CONCLUSIONS: The anti-P-12034/uPAR combination could be useful for identifying clinical TB patients. Such an approach holds promise for further validation.

Patients exposed to Mycobacterium tuberculosis infection with a prominent IgE response.

BACKGROUND AND AIMS: Even though it has been reported that chronic immune activation associated with intestinal helminthic infections results in a predominant IgE response, specific IgE antibodies that are also interleukin 4 (IL-4) dependent have been reported in tuberculosis patients; however, this fact has not been widely reported. This study was aimed at investigating the levels of circulating IgE in Warao (an indigenous population) of the Orinoco river delta, an area isolated from contact with the tubercle bacillus for millennia until the mid-1960s as compared to Creole (nonindigenous population). METHODS: A total of 294 individuals were studied, 161 Warao and 136 Creole. Patient group was comprised of 86 Warao patients (WP) and 60 Creole patients (CP). Control group was comprised of 75 Warao controls (WC) and 76 Creole controls (CC). Total serum IgE and IgE and IgG(4) reactivities to M. tuberculosis antigens were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of total serum IgE were significantly elevated in WP (13002.0 ± 11200.0 IU/mL) and WC (2763.5 ± 2596.2 IU/mL) than in CP (385.9 ± 155.1 IU/mL) and CC (356.6 ± 157.5 IU/mL) (p <0.0001). Anti-PPD and anti-H37Rv IgE were significantly higher in WP (0.240 ± 0.145 and 0.230 ± 0.155) than in CP (0.127 ± 0.152 and 0.97 ± 0.103, respectively) and also between WC (0.240 ± 0.273 and 0.147 ± 0.158) and CC (0.115 ± 0.136 and 0.43 ± 0.46, respectively) (p <0.0001). Anti-PPD and anti-H37Rv IgG(4) did not show differences among groups; however, anti-H37Rv IgG(4) was affected by anti-TB treatment, which could be predictive of treatment outcome. CONCLUSIONS: The findings suggest that for the Warao population there is an intrinsic propensity to produce a high IgE response, which could be incompatible with the protective response to M. tuberculosis.

The secretory immunoglobulin A response to Mycobacterium tuberculosis in a childhood population.

We report on the measurement of saliva anti-Purified Protein Derivative sIgA and 38kDa antibodies from 127 children, of whom 31 were strong tuberculosis suspects and 96 were healthy contact children. The results concerning the percentage of children with antibody reactivity to PPD and 38kDa antigens showed that, of these 2 antigens, 38kDa induced higher reactivity in patients positive and negative for the Tuberculin Skin Test (28% and 16.6%, respectively) in comparison to controls positive and negative for the TST (11.7% and 7.1%, respectively). There was a statistically significant difference between patients positive and controls negative for the TST. In relation to the Purified Protein Derivative antigen, while 14.2% of patients positive for the TST showed antibody reactivity to the PPD antigen, no patients negative for the TST had reactivity to this antigen. The findings suggest that these two antigens seem be associated with a different development of the mucosal defence mechanisms mediated by sIgA against Mycobacterium tuberculosis.