Diagnostic accuracy of IL-2 for the diagnosis of latent tuberculosis: a systematic review and meta-analysis

Abstract

We conducted a systematic review and meta-analysis to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarkers for the diagnosis of latent tuberculosis. Related studies were identified through searches of PubMed, Embase, Web of Science, and complementary manual searches up to December 30, 2013. We used standard methods recommended for meta-analyses of diagnostic test evaluations. The analysis was based on a summary receiver operating characteristic (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of the meta-analysis. The potential presence of publication bias was tested using the Deeks' funnel plots. The pooled estimates of IL-2 for latent tuberculosis infection (LTBI) diagnosis were as follows: sensitivity, 0.81 [95 % confidence interval (CI), 0.60 to 0.92]; specificity, 0.95 (95 % CI, 0.90 to 0.97); positive likelihood ratio (PLR), 15.2 (95 % CI, 8.1to 28.4); negative likelihood ratio (NLR), 0.20 (95 % CI, 0.09 to 0.47). We found that the SROC curve is positioned near the upper left corner of the curve and the area under the curve (AUC) was 0.96 (95 % CI, 0.94 to 0.98). In conclusion, according to the meta-analysis, IL-2 is a valid marker for the diagnosis of LTBI. When there is no definite gold standard for the diagnosis of LTBI, IL-2 release assay in addition to interferon-gamma release assays (IGRAs) can improve the ability of IGRAs to identify individuals with LTBI.

Evaluation of cytokine and chemokine response elicited by Rv2204c and Rv0753c to detect latent tuberculosis infection

“…All these selected cytokine/chemokines are known to play a major role in TB diagnostics. Previous reports show that IFN-c, IL-6, IL-8 [11,19], IL-10, IL-12p40 [20] and IL-2 [21] were associated with LTBI. On the other hand, TNF-a [22,29], IP-10 and MCP-2 [9] were more associated with active TB.…”

Novel T-Cell Assays for the Discrimination of Active and Latent Tuberculosis Infection: The Diagnostic Value of PPE Family

“…This study evaluated the diagnostic performance of IL-2 following stimulation with recombinant PE35 and PPE68 for the discrimination of active and latent TB. According to our previous meta-analysis, the sensitivity of the IL-2 assay following stimulation with TB antigen of QFT-G-IT test for diagnosis of LTBI ranged from 43 to 100 %, and the specificity of this marker was in the range from 89 to 100 % [31]. The pooled values of sensitivity (0.81) and specificity (0.95) showed the favorable accuracy of IL-2 for the detection of LTBI [31].…”

“…Among those IFNc and IL-2 T helper-1 (Th1) cytokines are of key importance for effective control of M. tuberculosis [25]. Several studies have demonstrated that IL-2 release, after stimulation by TBspecific antigens, was significantly higher in infected patients with TB than healthy controls [26][27][28][29][30], and suggested that IL-2 could be a potential biomarker for diagnosing LTBI infection [31,32].…”

“…According to our previous meta-analysis, the sensitivity of the IL-2 assay following stimulation with TB antigen of QFT-G-IT test for diagnosis of LTBI ranged from 43 to 100 %, and the specificity of this marker was in the range from 89 to 100 % [31]. The pooled values of sensitivity (0.81) and specificity (0.95) showed the favorable accuracy of IL-2 for the detection of LTBI [31]. In our study, the IL-2 profile induced by PE35 and PPE68 antigens in latently infected individuals was significantly higher than patients with active TB.…”

Discriminating between latent and active tuberculosis: The role of interleukin-2 as biomarker

“…3 No definite risk factors were identified in this study however the total number of recurrences is too small for accurate statistical analysis. Local HIV prevalence is up to 3.8 per 1000 10 with black Africans being at greater risk; the majority of the patients are South Asian.…”