Cytokine responses induced by Mycobacterium tuberculosis in patients with HIV-1 infection and tuberculosis

Oh, Myoung Don; Kang, Cheol In; Kim, Ui Seok; Kim, Nam Joong; Lee, Bobin; Kim, Hong Bin; Choe, Kang Won

doi:10.1016/j.ijid.2004.05.009

Cited by 6 publications

(5 citation statements)

References 20 publications

(24 reference statements)

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“…Despite an extensive literature that suggests that IFN-γ responses to mycobacterial antigens are decreased but detectable in HIV-infected individuals [8,10,14,26,27], we did not see differences in IFN-γ responses in subjects with and without TB. One reason for this discrepancy may be differential assay duration.…”

Section: Discussioncontrasting

confidence: 99%

“…Another potential reason for the discrepant IFN-γ results in this study is that certain mycobacterial antigens may be more efficient at generating IFN-γ responses than others. Commercially available assays of IFN-γ target ESAT-6 as well as CFP-10 with and without TB7.7 [4,25], and others have demonstrated detectable IFN-γ responses in HIV-infected subjects with active TB using purified protein derivative (PPD) [8,14] Our assay, which assessed responses to ESAT-6, Ag85 and WCL, may be less likely to generate IFN-γ responses that distinguish between subjects with and without TB. At a minimum, our data suggest that incubation period and antigen choice are critical variables in IFN-γ assays for TB.…”

Section: Discussionmentioning

confidence: 99%

“…Interferon gamma (IFN-γ) release assays (IGRA) are under active investigation for the diagnosis of latent and active TB [4-7]. Since diminished IFN-γ release is a cardinal antimycobacterial immune defect in HIV-infected people [8-14], and vulnerability to active TB in HIV-infected people increases with increasing immunodeficiency [15], HIV-related immunodeficiency has the potential to compromise IGRA accuracy. Thus, it will be important to investigate additional methods of diagnosing latent and active TB.…”

Section: Introductionmentioning

confidence: 99%

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Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis

Lahey¹,

Matee

Mtei

et al. 2009

BMC Infect Dis

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BackgroundIdentifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA) in HIV-infected subjects with latent or active TB.MethodsHIV-infected subjects with bacille Calmette Guérin (BCG) scars and CD4 counts ≥ 200 cells/mm3 entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST), LPA and five day assays of interferon gamma (IFN-γ) release. Assay antigens were early secreted antigenic target 6 (ESAT-6), antigen 85 (Ag85), and Mycobacterium tuberculosis whole cell lysate (WCL). Subjects were screened for active TB at enrollment by history, exam, sputum smear and culture. We compared antimycobacterial immune responses between subjects with and without latent or active TB at enrollment.ResultsAmong 1885 subjects screened, 635 had latent TB and 13 had active TB. Subjects with latent TB were more likely than subjects without TB to have LPA responses to ESAT-6 (13.2% vs. 5.5%, P < 0.0001), Ag85 (18.7% vs. 3.1%, P < 0.0001), and WCL (45.7% vs. 17.1%, P < 0.0001). Subjects with active TB also were more likely than those without active TB to have detectable LPA responses to ESAT-6 (38.5% vs. 8.1%, P = 0.0001), Ag85 (46.2% vs. 8.5%, P < 0.0001), and WCL (61.5% vs. 27.0%, P = 0.0053). In subjects with a positive TST, LPA responses to ESAT-6, Ag85 and WCL were more common during active TB (p < 0.0001 for all tests). In diagnosing active TB, in vivo and in vitro tests of mycobacterial immune responses had sensitivity and specificity as follows: TST 84.6% and 65.5%, ESAT-6 LPA 38.5% and 92.0%, Ag85 LPA 46.2% and 91.5%, and WCL LPA 61.5% and 73.0%. Detectable LPA responses were more common in patients with higher CD4 counts, and higher HIV viral loads.ConclusionLymphoproliferative responses to mycobacteria are detectable during HIV-associated active TB, and are less sensitive but more specific than TST.Trial registrationClinicalTrials.gov Identifier NCT00052195.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis

Lahey¹,

Matee

Mtei

et al. 2009

BMC Infect Dis

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“…It has been suggested that specific T cell responses in TB patients with advanced immunosuppression are impaired [12]. However, this is not supported by several other studies [13,14,15]. Blood-based IFN-γ assays are fast becoming the standard for diagnosing latent TB and are now performed in an increasing number of laboratories worldwide.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Adapted Whole-Blood Interferon-γ Release Assays for the Diagnosis of Pleural Tuberculosis

Chegou

Walzl²,

Bolliger³

et al. 2008

Respiration

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Background: Pleural tuberculosis (TB) remains difficult to diagnose despite numerous diagnostic tools. Recently, in vitro interferon (IFN)-γ-based assays have been introduced in the diagnosis of latent TB, but these techniques have not been established in the diagnosis of active TB disease, including pleural TB. Objectives: It was the aim of this study to assess the accuracy of the commercially available QuantiFERON® TB Gold assay and adapted variants of the assay, using pleural fluid or isolated pleural fluid cells for the diagnosis of pleural TB. Methods: We recruited 66 consecutive patients with a pleural effusion of unknown cause presenting at a tertiary academic health care centre in Cape Town, South Africa, a high prevalence area of TB. Blood and pleural fluid were collected at presentation for IFN-γ assays and the results evaluated for diagnostic accuracy. Results: The clinical diagnosis was TB in 30 (46%), malignancy in 20 (30%), parapneumonic effusion/empyema in 8 (12%) and effusion due to other causes in 8 patients (12%). Ex vivo pleural fluid IFN-γ levels accurately identified TB in all patients and were superior to the QuantiFERON In Tube assay using blood and pleural fluid (73 and 57% sensitivity, with 71 and 87% specificity, respectively) and the QuantiFERON Gold assay applied to isolated pleural fluid cells (100% sensitivity and 67% specificity). Conclusion: The ex vivo pleural fluid interferon-γ level is an accurate marker for the diagnosis of pleural TB, and the QuantiFERON TB Gold assay performed with peripheral blood or adapted for pleural fluid cells does not add diagnostic value.

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“…In HIV infection, IFN-g plays a vital role in the reduction of HIV replication. It was shown that the progression of immunodeficiency was associated with diminished IFN-g production [40,41]. Also, IFN-g has a major role in protecting against TB [38,42,43].…”

Section: Introductionmentioning

confidence: 99%

Decreased IL-1 β Secretion as a Potential Predictor of Tuberculosis Recurrence in Individuals Diagnosed with HIV

Nosik,

Ryzhov,

Kudryavtseva

et al. 2024

Biomedicines

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Background: The mechanisms of the formation of immunological competence against tuberculosis (TB), and especially those associated with HIV co-infection, remain poorly understood. However, there is an urgent need for risk recurrence predictive biomarkers, as well as for predictors of successful treatment outcomes. The goal of the study was to identify possible immunological markers of TB recurrence in individuals with HIV/TB co-infection. Methods: The plasma levels of IFN-γ, TNF-α, IL-10, and IL-1β (cytokines which play important roles in the immune activation and protection against Mycobacterium tuberculosis) were measured using ELISA EIA-BEST kits. The cytokine concentrations were determined using a standard curve obtained with the standards provided by the manufacturer of each kit. Results: A total of 211 individuals were enrolled in the study as follows: 62 patients with HIV/TB co-infection, 52 with HIV monoinfection, 52 with TB monoinfection, and 45 healthy donors. Out of the 62 patients with HIV/TB, 75.8% (47) of patients were newly diagnosed with HIV and TB, and 24.2% (15) displayed recurrent TB and were newly diagnosed with HIV. Decreased levels of IFN-γ, TNF-α, and IL-10 were observed in patients with HIV/TB when compared with HIV and TB patients. However, there was no difference in IFN-γ, TNF-α, or IL-10 secretion between both HIV/TB groups. At the same time, an almost 4-fold decrease in Il-1β levels was detected in the HIV/TB group with TB recurrence when compared with the HIV/TB group (p = 0.0001); a 2.8-fold decrease when compared with HIV patients (p = 0.001); and a 2.2-fold decrease with newly diagnosed TB patients (p = 0.001). Conclusions: Significantly decreased Il-1β levels in HIV/TB patients’ cohort with secondary TB indicate that this cytokine can be a potential biomarker of TB recurrence.

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Cytokine responses induced by Mycobacterium tuberculosis in patients with HIV-1 infection and tuberculosis

Abstract: Cytokine responses to M. tuberculosis were retained in HIV-infected patients with tuberculosis, even in patients with a CD4 cell count of less than 200/mm3, and reconstituted after HAART.

Cited by 6 publications

References 20 publications

Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis

Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis

Evaluation of Adapted Whole-Blood Interferon-γ Release Assays for the Diagnosis of Pleural Tuberculosis

Decreased IL-1 β Secretion as a Potential Predictor of Tuberculosis Recurrence in Individuals Diagnosed with HIV

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