Antigen-Specific T-Cell Activation Distinguishes between Recent and Remote Tuberculosis Infection.
Am J Respir Crit Care Med
; 203(12): 1556-1565, 2021 06 15.
Article
em En
| MEDLINE
| ID: mdl-33406011
ABSTRACT
Rationale Current diagnostic tests fail to identify individuals at higher risk of progression to tuberculosis disease, such as those with recent Mycobacterium tuberculosis infection, who should be prioritized for targeted preventive treatment. Objectives:
To define a blood-based biomarker, measured with a simple flow cytometry assay, that can stratify different stages of tuberculosis infection to infer risk of disease.Methods:
South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 mo) and persistent (QuantiFERON-TB+ for >1 yr) infection. We defined the ΔHLA-DR median fluorescence intensity biomarker as the difference in HLA-DR expression between IFN-γ+ TNF+Mycobacterium tuberculosis-specific T cells and total CD3+ T cells. Biomarker performance was assessed by blinded prediction in untouched test cohorts with recent versus persistent infection or tuberculosis disease and by unblinded analysis of asymptomatic adolescents with tuberculosis infection who remained healthy (nonprogressors) or who progressed to microbiologically confirmed disease (progressors). Measurements and MainResults:
In the test cohorts, frequencies of Mycobacterium tuberculosis-specific T cells differentiated between QuantiFERON-TB- (n = 25) and QuantiFERON-TB+ (n = 47) individuals (area under the receiver operating characteristic curve, 0.94; 95% confidence interval, 0.87-1.00). ΔHLA-DR significantly discriminated between recent (n = 20) and persistent (n = 22) QuantiFERON-TB+ (0.91; 0.83-1.00); persistent QuantiFERON-TB+ and newly diagnosed tuberculosis (n = 19; 0.99; 0.96-1.00); and tuberculosis progressors (n = 22) and nonprogressors (n = 34; 0.75; 0.63-0.87). However, ΔHLA-DR median fluorescent intensity could not discriminate between recent QuantiFERON-TB+ and tuberculosis (0.67; 0.50-0.84).Conclusions:
The ΔHLA-DR biomarker can identify individuals with recent QuantiFERON-TB conversion and those with disease progression, allowing targeted provision of preventive treatment to those at highest risk of tuberculosis. Further validation studies of this novel immune biomarker in various settings and populations at risk are warranted.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Biomarcadores
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Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral
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Tuberculose Latente
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Mycobacterium tuberculosis
Tipo de estudo:
Etiology_studies
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Incidence_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Africa
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
África do Sul