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Pathogenesis of Tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Divya B. Reddy, Jerrold J. Ellner
Immunosuppression makes the diagnosis of TB in persons living with HIV challenging. Several biosignatures that can accurately detect active TB from other lung diseases in HIV-infected individuals have now been identified.269–273 Differential gene expression of activating Fcγ receptor (FcGR1A) is of particular interest as it has been shown to successfully distinguish active TB from latent TB regardless of HIV status or genetic background.274 Gene expression of BATF2 has also been shown to have a high-negative predictive value in diagnosing active TB-coinfected individuals.275 In fact, recently Verma et al. have shown that gene expression of FcGR1A and BATF2 in addition to plasma protein levels of IFN-γ and CXCL10 have the potential to identify active TB even in advanced HIV patients with a CD4 count of <100 cells/μL).276
Utility of a three-gene transcriptomic signature in the diagnosis of tuberculosis in a low-endemic hospital setting
Published in Infectious Diseases, 2023
Bih Hycenta Chendi, Tracey Jooste, Thomas Jens Scriba, Martin Kidd, Simon Mendelsohn, Kristian Tonby, Gerhard Walzl, Anne M. Dyrhol-Riise, Novel Njweipi Chegou
Most of the genes identified so far have been largely linked to pathway patterns associated with TB, of which the Type 1 interferon signalling pathway represents the most outstanding via the expression of interferon-stimulating genes (ISG) [9]. These interferon-stimulating genes are essential in stimulating or inhibiting immune function. Of the three individual genes (BAFT2, ETV7, CD1C) encompassing the newly identified signature, only BATF2 is induced by type 1 interferons [23,38,39]. BATF2 belongs to a family of activating transcription factor proteins and was observed to be involved in the regulation of transcription and mediating downstream proinflammatory responses [23,40] following its interactions with interferon regulatory factor-1 (IRF1). Although Upper respiratory infections are likely to have an impact on the expression of any interferon-stimulated genes, as seen in the study by Mendelsohn et al. [41], the absence of potential interferon-stimulating genes in the identified signature might be due to the presence of lower respiratory infections used as controls in this study. This corroborates with studies highlighting the existence of a distinct transcriptional profile differentiating viral and bacterial infection at the level of host response [42–44]. While it is important to distinguish TB disease from other respiratory infections in individuals who are clinically reasonable suspects of TB, further investigation and making use of specific viral or bacterial infections in different cohorts might help in identifying a unique signature and pathway for diagnosing TB. Given the potential challenges involved in the translation of large gene signatures into point-of-care platforms, the identification of smaller gene sets has been encouraged. Similar three-gene signatures with potential in the diagnosis of TB have been previously identified in low TB endemic settings [14,45,46]. Results from a prototype three-gene-based test showed potential among African study participants that were enrolled in primary healthcare settings with pulmonary TB [47]. As such, the signature identified in this study thus holds promise for translation into similar point-of-care devices for potential use both in low and high TB endemic settings, including individuals with extrapulmonary TB if the promising accuracy observed in the current study is maintained in future larger studies.