ArticleInfection and drug resistance2021
Increased Expression of IL-10 in Peripheral Blood Mononuclear Cells Correlates with Negative Interferon-γ Release Assay Results in Culture-Confirmed Tuberculosis Patients.
Article in Infection and drug resistance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed, 5 citations in OpenAlex.
- Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection.Tropical medicine and infectious disease · 2023Review
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7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionInterferon-γ release assays (IGRAs) can have high false-negative rates for active tuberculosis (TB) cases. Here we investigated factors, including potential anti-inflammatory mechanisms, that contributed to false-negative IGRA results.
methodsWe established two cohorts. In the first cohort, we reviewed IGRA results for confirmed TB cases diagnosed in our hospital in 2018. Cases with false-negative IGRA results were analysed to identify factors contributing to false-negative results. In the second cohort, we prospectively studied IL-10 expression levels in peripheral blood mononuclear cells (PBMCs) of IGRAs-positive and IGRAs-negative TB cases after antigenic stimulation to correlate IL-10 expression with IGRAs results.
resultsOf 1232 culture-confirmed TB cases, 1124 produced true-positive IGRA results and 108 had false-negative IGRA results. Multivariate logistic regression analysis identified glucocorticoid use and extrapulmonary TB as independent risk factors for false-negative IGRA results. Notably, IL-10 expression of the IGRA-negative group was significantly up-regulated as compared to that of the IGRA-positive group. The average cell supernatant IL-10 concentration of the IGRA-negative group was 4.77 pg/mL, a value that was statistically greater than the IGRA-positive group concentration (1.47 pg/mL, P = 0.007). After PBMCs pretreatment with BRD6989 (to enhance IL-10 secretion), average IFN-γ concentrations in cell supernatants from the IGRA-positive group significantly decreased from 59.73 pg/mL to 33.79 pg/mL (P = 0.011). By contrast, addition of AS101 (to inhibit IL-10 secretion) to false-negative group PBMCs led to an increase of average IFN-γ concentration in cell supernatants from 19.01 pg/mL to 45.10 pg/mL (P = 0.030), a result that was inversely correlated with IL-10 concentration.
conclusionOur data demonstrate that increased IL-10 secretion by PBMCs is inversely correlated with IGRA assay results in culture-confirmed TB patients. Glucocorticoids use and extrapulmonary TB are significantly associated with false-negative IGRA results. Combination testing to measure IL-10 secretion and IFN-γ release is recommended to improve IGRAs specificity.
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