Blood and urine inducible protein 10 as potential markers of disease activity

Petrone, Linda; Cannas, Angela; Vanini, Valentina; Cuzzi, Gilda; Aloi, Francesco; Nsubuga, Martin; Sserunkuma, J.; Nazziwa, Ritah Angella; Jugheli, Levan; Lukindo, Tedson; Girardi, Enrico; Antinori, Andrea; Pucci, Luigia; Reither, Klaus; Goletti, Delia

doi:10.5588/ijtld.16.0342

Cited by 44 publications

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“…In this study we showed for the first time that IP-10 agonist and antagonist forms may be detected in urine. In line with our and other publications (Cannas et al, 2010;Petrone et al, 2015;Petrone et al, 2016), we confirmed that IP-10 is increased in the urine of patients with active TB but also in diseases different from TB such as pneumonia. Moreover, we demonstrated that levels of agonist Figure 1.…”

Section: Discussionsupporting

confidence: 93%

“…IP-10 may be released by infected alveolar macrophages promoting the migration of Th1 cells to the site of infection (Kaufmann and Dorhoi, 2013;Lindestam Arlehamn et al, 2013;Moguche et al, 2017;O'Garra et al, 2013;Saha et al, 2013) through binding to CXCR3 expressed on T cells. Moreover, IP-10 is increased in plasma and urine of active TB patients (Goletti et al, 2010a;Goletti et al, 2010b;Vanini et al, 2012) and decreases after efficacious therapy (Azzurri et al, 2005;Chegou et al, 2013;Cannas et al, 2010), correlates with risk of progression to disease and TB disease severity (Azzurri et al, 2005;Petrone et al, 2018;Riou et al, 2012) and is easily detected as an inflammatory marker in both adults and children (Petrone et al, 2015;Petrone et al, 2016;Santos et al, 2018). Importantly, IP-10 is a key player in trained immunity, a protection phenomenon dependent on epigenetic modifications of monocytes (Joosten et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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First description of agonist and antagonist IP-10 in urine of patients with active TB

Petrone

Bondet

Vanini

et al. 2019

International Journal of Infectious Diseases

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

First description of agonist and antagonist IP-10 in urine of patients with active TB

Petrone

Bondet

Vanini

et al. 2019

International Journal of Infectious Diseases

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“…Interestingly, IP‐10 was also detected in the urine of adult patients and Ugandan children with active TB, and IP‐10 levels decreased following efficacious therapy . As has been recently suggested, however, IP‐10 should probably be considered as a marker of general inflammation …”

Section: Bm For Diagnosing Active Tbmentioning

confidence: 76%

“…22 As has been recently suggested, however, IP-10 should probably be considered as a marker of general inflammation. 51,52 As mentioned above, the use of urine or saliva offers the advantage of noninvasive and ease to handle sampling. It has been reported that saliva levels of interleukin (IL)-1β, IL-23, ECM-1, HCC1 and fibrinogen are significantly associated with active TB.…”

Section: Bm For Diagnosing Active Tb: Immune Protein Host Signatures mentioning

confidence: 99%

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

et al. 2018

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Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB-BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB-BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB-BM currently studied are host-derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations ('signatures'). In particular, vaccine-inducible CoP are expected to be transformative in developing new TB vaccines as they will de-risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals. Of key importance is that TB-BM are tested and validated in different well-characterized human TB cohorts, preferably with complementary profiles and geographically diverse populations: genetic and environmental factors such as (viral) coinfections, exposure to non-tuberculous mycobacteria, nutritional status, metabolic status, age (infants vs children vs adolescents vs adults) and other factors impact host immune set points and host responses across different populations. In this study, we review the most recent advances in research into TB-BM for the diagnosis of active TB, risk of TB development and treatment-induced TB cure.

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“…Our results cannot be generalized to the testing of HIV-infected children, in whom the assay has unfortunately not been found to have utility [34]. Ongoing research on pathogen and host diagnostic urine biomarkers for TB may yield urine assays with improved performance characteristics in the future [35–37]. …”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort

Lawn

Kerkhoff

Burton

et al. 2017

BMC Med

105

100

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BackgroundWe previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB.MethodsSputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions.ResultsConsecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9–99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50–11.75).ConclusionsRoutine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0822-8) contains supplementary material, which is available to authorized users.

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Blood and urine inducible protein 10 as potential markers of disease activity

Abstract: These findings suggest that IP-10 could be used as a biomarker for disease activity (inflammation).

Cited by 44 publications

References 0 publications

First description of agonist and antagonist IP-10 in urine of patients with active TB

First description of agonist and antagonist IP-10 in urine of patients with active TB

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort

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