3 research outputs found
Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals
CITATION: Manngo, P. M. et al. 2019. Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals. Journal of Infection, 79(3):228-235, doi:10.1016/j.jinf.2019.07.007.The original publication is available at https://www.journalofinfection.comBackground: There is an urgent need for new tools for the diagnosis of TB. We evaluated the usefulness recently described host biomarkers in supernatants from the newest generation of the QuantiFERON test (QuantiFERON Plus) as tools for the diagnosis of active TB. Methods: We recruited individuals presenting at primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease, prior to the establishment of a clinical diagnosis. Participants were later classified as TB or other respiratory diseases (ORD) based on the results of clinical and laboratory tests. Using a multiplex platform, we evaluated the concentrations of 37 host biomarkers in QuantiFERON Plus supernatants from study participants as tools for the diagnosis of TB. Results: Out of 120 study participants, 35(29.2%) were diagnosed with active TB, 69(57.5%) with ORD whereas 16(13.3%) were excluded. 14(11.6%) of the study participants were HIV infected. Although individ- ual host markers showed potential as diagnostic candidates, the main finding of the study was the identi- fication of a six-marker biosignature in unstimulated supernatants (Apo-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56) which diagnosed TB with sensitivity and specificity of 73.9%(95% CI; 51.6–87.8) and 87.6%(95% CI; 77.2–94.5), respectively, after leave-one-out cross validation. Combinations between TB-antigen specific biomarkers also showed potential (sensitivity of 77.3% and specificity of 69.2%, respectively), with multi- ple biomarkers being significantly different between TB patients, Quantiferon Plus Positive and Quantif- eron Plus negative individuals with ORD, regardless of HIV status. Conclusions: Biomarkers detected in QuantiFERON Plus supernatants may contribute to adjunctive diag- nosis of TB.EDCTP , grant no: DRIA2014-311National Research FoundationICIDR (grant no: 5U01IA115619)Publisher's versio
Performance and immune characteristics of bronchoalveolar lavage by research bronchoscopy in pulmonary tuberculosis and other lung diseases in the Western Cape, South Africa
CITATION: Young, C., et al. 2019. Performance and immune characteristics of bronchoalveolar lavage by research bronchoscopy in pulmonary tuberculosis and other lung diseases in the Western Cape, South Africa. Translational Medicine Communications, 4:7, doi:10.1186/s41231-019-0039-2.The original publication is available at https://transmedcomms.biomedcentral.comBackground: Tuberculosis (TB) remains a debilitating, deadly disease that warrants innovative research tools to fully
understand the pathogenesis and host immune responses, particularly at the site of infection and disease. In this
regard, bronchoscopies with bronchoalveolar lavage (BAL) serve as a valuable technique for site of disease sample
retrieval for further clinical- and basic research. Here we investigate the feasibility of research bronchoscopies in a
low/middle-income area, where TB remains rife, and assess the value of retrieved BAL cells (BALC) for downstream
fluorescent-based cellular evaluations.
Methods: Using quantitative and qualitative methods, we evaluate the outcomes, safety, tolerability, participant
-perception and -experience, while also providing insight into participant recruitment and screening processes of
our study. Using light microscopy differential counting for BALC analysis, we evaluate the cellular composition of
BAL fluid (BALF) from TB patients, healthy community controls and patients with other lung diseases. We also use
flow cytometry to describe the challenges associated with fluorescence-based phenotypic analysis of
autofluorescent BALC.
Results: Our findings suggest that research bronchoscopies are safe, acceptable procedures for research
participants and are indeed a feasible technique for future study design. We also suggest that the majority of
participants are receptive to the proposition of a second research bronchoscopy. This poses an important avenue
for research entailing follow-up investigations of the same study participant. Furthermore, our results show that
smoking is characterized by retrieval of BALC containing particulate matter, that interferes with fluorescence-based
flow cytometry data analysis. Based on light microscopy differential cell counting, our findings suggest that there
are differences in the cell yields and cellular composition of the BALF between TB patients, healthy community
controls and patients with other lung diseases. We also report on subject characteristics and demographic factors,
namely gender and age, that have the potential to affect cell yields and cellular data of BALF.
Conclusions: These findings will serve as a valuable reference for appropriate planning and design of studies
involving clinical bronchoscopies for TB and lung disease research.doi:10.1186/s41231-019-0039-2https://transmedcomms.biomedcentral.com/articles/10.1186/s41231-019-0039-2Publisher's versio
GPR183 regulates interferons, autophagy, and bacterial growth during Mycobacterium tuberculosis infection and is associated with TB disease severity
Oxidized cholesterols have emerged as important signaling molecules of immune function, but little is known about the role of these oxysterols during mycobacterial infections. We found that expression of the oxysterol-receptor GPR183 was reduced in blood from patients with tuberculosis (TB) and type 2 diabetes (T2D) compared to TB patients without T2D and was associated with TB disease severity on chest x-ray. GPR183 activation by 7α,25-dihydroxycholesterol (7α,25-OHC) reduced growth of\ua0Mycobacterium tuberculosis\ua0(Mtb) and\ua0Mycobacterium bovis\ua0BCG in primary human monocytes, an effect abrogated by the GPR183 antagonist GSK682753. Growth inhibition was associated with reduced IFN-β and IL-10 expression and enhanced autophagy. Mice lacking GPR183 had significantly increased lung Mtb burden and dysregulated IFNs during early infection. Together, our data demonstrate that GPR183 is an important regulator of intracellular mycobacterial growth and interferons during mycobacterial infection