IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions

Rühwald, Morten; Aabye, Martine G.; Ravn, Pernille

doi:10.1586/erm.11.97

Cited by 119 publications

(127 citation statements)

References 111 publications

(79 reference statements)

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“…In addition, chemokines and their receptors, including IP-10, contribute to the formation and maintenance of granulomas in TB (33). IP-10 plays a role in M. tuberculosis infection, and several studies have shown that antigenstimulated IP-10 responses have a sensitivity similar to that of QFT-GIT for detecting active TB (12,13,34,35). Our results also showed a higher level of IP-10 in active TB patients, consistent with previously published studies; IP-10 can therefore serve as a potential diagnostic biomarker.…”

Section: Discussionsupporting

confidence: 91%

Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

et al. 2015

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f Mycobacterium tuberculosis is the major causative agent of tuberculosis (TB). The gamma interferon (IFN-␥) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied to the commercial IFN-␥ release assay, QuantiFERON-TB Gold In-Tube, and plasma samples were analyzed for interleukin-2 (IL-2), IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNF-␣), IFN-␥, monokine induced by IFN-␥ (MIG), interferon gamma inducible protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant (I-TAC), and monocyte chemoattractant protein 1 (MCP-1) by using a commercial cytometric bead array. The Mycobacterium tuberculosis antigen-specific production of most of the assayed cytokines and chemokines was higher in the active TB than in the LTBI group. The mitogen-induced responses were lower in the active TB than in the LTBI group. When the ratio of TB-specific to mitogen-induced responses was calculated, IL-2, IL-6, IL-10, IL-13, TNF-␣, IFN-␥, MIG, and IP-10 were more useful in discriminating active TB from LTBI. In particular, most patients showed higher IP-10 production to Mycobacterium tuberculosis antigens than to mitogen at the individual level, and the ratio for IP-10 was the strongest indicator of active infection versus LTBI with 93.9% sensitivity and 90% specificity. In conclusion, the ratio of the TB-specific to the mitogen-induced IP-10 responses showed the most promising accuracy for discriminating active TB versus LTBI and should be further studied to determine whether it can serve as a biomarker that might help clinicians administer appropriate treatments. M ycobacterium tuberculosis, the major causative agent for tuberculosis (TB), is among the most successful human pathogens, infecting approximately 8.6 million people and leading to 1.3 million deaths each year (1). It is estimated that 2 billion people live with latent TB infection (LTBI) and are therefore a potential source of active TB (2, 3). Identifying LTBI is necessary in order to reduce the risk of development of the disease, while diagnosis of active TB can enable rapid treatment and disease control. To this end, diagnostic biomarkers that can accurately indicate disease status are needed (4, 5).There is presently no diagnostic gold standard for LTBI. Until recently, the tuberculin skin test (TST) involving the intracutaneous injection of purified protein derivative (PPD) into the forearm was the only available method for diagnosing LTBI. However, PPD cross-reacts with nontuberculous mycobacteria as well as with Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine and has poor sensitivity in immunocompromised patients (6). The interferon gamma (IFN-␥) release assay (IGRA) has been widely used in clinical practice a...

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Section: Discussionsupporting

confidence: 91%

Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

et al. 2015

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“…22 Multiple alternative cutoffs for IP-10 have been suggested (reviewed in ref. 11), and a larger study is currently ongoing to validate the cutoff (M. Ruhwald, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…Test results were classified as positive, negative, or indeterminate according to current diagnostic algorithms for QFT and IP-10 release assays. 11,21 For determining the QFT or IP-10 test results, the cytokine level from the unstimulated sample is subtracted from the cytokine level in the antigen and mitogen samples.…”

Section: Methodsmentioning

confidence: 99%

“…11 IP-10 is secreted by antigen-presenting cells interacting with T cells recognizing Mtb-specific peptides presented on its surface. 12 IP-10 release assays perform on par with the commercially available IGRA QuantiFERON ® -TB (Cellestis Ltd., Carnegie, Victoria, Australia) Gold In-Tube (QFT) test, 11,12 but contrary to the QFT, IP-10 release assays appear less affected by immunosuppression such as a low CD4-cell count in HIV-infected individuals 4,5 and in young-aged children. 13,14 Malaria and tuberculosis (TB) are co-endemic in most of sub-Saharan Africa.…”

Section: Introductionmentioning

confidence: 99%

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Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

Drabe

Vestergaard

Helleberg

et al. 2016

The American Journal of Tropical Medicine and Hygiene

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Abstract. Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis. The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD ® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem ® ). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.

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“…Moreover, measurement of different soluble molecules such as cytokines or chemokines or cytotoxic molecules in addition to IFN-␥ has also been proposed as a way of improving the diagnostic sensitivity of IGRAs [25]. Very recently, a review of 22 studies investigated on the role of IP-10 in TB diagnosis empathizing that its levels may be used to better detect TB infection in young children and in people with TB-HIV coinfection, where usually the counts of CD4T cells are very low [26].…”

Section: Discussionmentioning

confidence: 99%

Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease

et al. 2015

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a b s t r a c tCytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI).Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425 pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively.Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-␥, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals.

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IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions

Cited by 119 publications

References 111 publications

Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease

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