Different Quantitative Interferon-γ Response in Active Tuberculosis of Various Primary Infection Sites
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Background: The quantitative interferon (IFN)-γ response in the IFN-γ release assay (IGRA) has been investigated to predict progression from Mycobacterium tuberculosis infection to active tuberculosis (TB). However, the significance of the quantitative IFN-γ response in active TB is rarely known. We assessed the association between IFN-γ response to nil, mitogen, and TB mycobacterial antigens, and the variations from serial IGRA testing in active TB of various primary infection sites. Methods: In total, 102 active TB patients with serial QuantiFERON-TB Gold In-Tube (QFT-GIT) (Qiagen, Germany) were enrolled. The medical records of patients were reviewed for demographic information, infection sites, tuberculosis treatment, and the quantitative IFN-γ response to nil, mitogen, and TB antigen. Results: Patients included 20, 68, and 14 cases of pulmonary TB, extrapulmonary TB, and multiple TB infection, respectively. The quantitative IFN-γ responses to TB antigens differed significantly according to the infection sites ( P =0.0001). The median IFN-γ response was the highest in lymph node infection (10.0 IU/mL) and the lowest in central nervous system (CNS) infection (0.02 IU/mL). Of the total, 86.3% showed concordant results in serial testing. Both 50% of the patients with persistent negative results and 62.5% of patients with CNS TB had an insufficient IFN-γ response to mitogen. Conclusions: Different IFN-γ responses to TB antigens may indicate variable host immune responses among infection sites in active TB disease. Because a few active TB patients fail to produce an adequate IFN-γ response, a study of cellular mechanisms is needed in such unresponsive patients.
Abstract
Background: The quantitative interferon (IFN)-γ response in the IFN-γ release assay (IGRA) has been investigated to predict progression from Mycobacterium tuberculosis infection to active tuberculosis (TB). However, the significance of the quantitative IFN-γ response in active TB is rarely known. We assessed the association between IFN-γ response to nil, mitogen, and TB mycobacterial antigens, and the variations from serial IGRA testing in active TB of various primary infection sites. Methods: In total, 102 active TB patients with serial QuantiFERON-TB Gold In-Tube (QFT-GIT) (Qiagen, Germany) were enrolled. The medical records of patients were reviewed for demographic information, infection sites, tuberculosis treatment, and the quantitative IFN-γ response to nil, mitogen, and TB antigen. Results: Patients included 20, 68, and 14 cases of pulmonary TB, extrapulmonary TB, and multiple TB infection, respectively. The quantitative IFN-γ responses to TB antigens differed significantly according to the infection sites ( P =0.0001). The median IFN-γ response was the highest in lymph node infection (10.0 IU/mL) and the lowest in central nervous system (CNS) infection (0.02 IU/mL). Of the total, 86.3% showed concordant results in serial testing. Both 50% of the patients with persistent negative results and 62.5% of patients with CNS TB had an insufficient IFN-γ response to mitogen. Conclusions: Different IFN-γ responses to TB antigens may indicate variable host immune responses among infection sites in active TB disease. Because a few active TB patients fail to produce an adequate IFN-γ response, a study of cellular mechanisms is needed in such unresponsive patients.
참고문헌 (34)
- Zumla A, "The WHO 2014 global tuberculosis report--further to go", Lancet Glob Health, 3, pp.e10~2 (2015)
- Thomas J. Scriba, "Human Immunology of Tuberculosis", Microbiology Spectrum, 5(1) (2017), American Society for Microbiology[DOI]
- Pai M, "Tuberculosis", Nat Rev Dis Primers, 2, pp.16076~ (2016)
- Mazurek GH, "Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection-United States, 2010", MMWR Recomm Rep, 59, pp.1~25 (2010)
- Andrews JR, "Serial QuantiFERON testing and tuberculosis disease risk among young children : an observational cohort study", Lancet Respir Med, 5, pp.282~290 (2017)
- Nemes E, "Optimization and interpretation of serial QuantiFERON testing to measure acquisition of Mycobacterium tuberculosis infection", Am J Respir Crit Care Med, 196, pp.638~648 (2017)
- Winje BA, "Stratification by interferon-γ release assay level predicts risk of incident TB", Thorax, 73, pp.652~661 (2018)
- Woo KS, "Significance of interferon-gamma response to mitogen in serial QuantiFERON-TB Gold In-Tube assay of routine laboratory practice", Clin Chim Acta, 430, pp.79~83 (2014)
- Huang HC, "The predictive value of the interferon-γ release assay for chemotherapy responses in patients with advanced non-small-cell lung cancer", Lung Cancer, 115, pp.64~70 (2018)
- Ahn SS, "Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus", Arthritis Res Ther, 19, pp.193~ (2017)
- Yong MK, "Low T-cell responses to mitogen stimulation predicts poor survival in recipients of allogeneic hematopoietic stem cell transplantation", Front Immunol, 8, pp.1506~ (2017)
- Marais S, "Tuberculous meningitis : a uniform case definition for use in clinical research", Lancet Infect Dis, 10, pp.803~812 (2010)
- 이지연, "Diagnosis and Treatment of Extrapulmonary Tuberculosis", Tuberculosis and Respiratory Diseases, 78(2), pp.47~55 (2015), 대한결핵및호흡기학회
- Kwan CK, "HIV and tuberculosis : a deadly human syndemic", Clin Microbiol Rev, 24, pp.351~376 (2011)
- Fan L, "Interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis : a systematic review and meta-analysis", FEMS Immunol Med Microbiol, 65, pp.456~466 (2012)
- Di L, "The risk factor of false-negative and false-positive for T-SPOT. TB in active tuberculosis", J Clin Lab Anal, 32, pp.e22273~ (2018)
- Cho OH, "Diagnostic performance of T-SPOT.TB for extrapulmonary tuberculosis according to the site of infection", J Infect, 63, pp.362~369 (2011)
- Chandra SR, "Factors determining the clinical spectrum, course and response to treatment, and complications in seronegative patients with central nervous system tuberculosis", J Neurosci Rural Pract, 8, pp.241~248 (2017)
- Auld SC, "IFN-γ release assay result is associated with disease site and death in active tuberculosis", Ann Am Thorac Soc, 13, pp.2151~2158 (2016)
- Blankley S, "The transcriptional signature of active tuberculosis refiects symptom status in extra-pulmonary and pulmonary tuberculosis", PLoS One, 11, pp.e0162220~ (2016)
- Berry MP, "An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis", Nature, 466, pp.973~977 (2010)
- Cadena AM, "Heterogeneity in tuberculosis", Nat Rev Immunol, 17, pp.691~702 (2017)
- Joshi M, "IFN-γ release assay conversions and reversions. Challenges with serial testing in U.S. health care workers", Ann Am Thorac Soc, 11, pp.296~302 (2014)
- Clifford V, "Interferon gamma release assays for monitoring the response to treatment for tuberculosis : A systematic review", Tuberculosis(Edinb), 95, pp.639~650 (2015)
- Kumar NP, "Expansion of pathogen-specific mono-and multifunctional Th1 and Th17 cells in multi-focal tuberculous lymphadenitis", PLoS One, 8, pp.e57123~ (2013)
- de Visser V, "False-negative interferon-γ release assay results in active tuberculosis : a TBNET study", Eur Respir J, 45, pp.279~283 (2015)
- Kwon YS, "Factors that predict negative results of QuantiFERON-TB Gold In-Tube test in patients with culture-confirmed tuberculosis : A multicenter retrospective cohort study", PLoS One, 10, pp.e0129792~ (2015)
- Nguyen DT, "Characteristics associated with negative interferon-γ release assay results in culture-confirmed tuberculosis patients, Texas, USA, 2013-2015", Emerg Infect Dis, 24, pp.534~540 (2018)
- Sester M, "Interferon-γ release assays for the diagnosis of active tuberculosis : a systematic review and meta-analysis", Eur Respir J, 37, pp.100~111 (2011)
- Aichelburg MC, "Prognostic value of indeterminate IFN-γ release assay results in HIV-1 infection", J Clin Microbiol, 50, pp.2767~2769 (2012)
- Lee EH, "Active tuberculosis incidence and characteristics in patients treated with tumor necrosis factor antagonists according to latent tuberculosis infection", Sci Rep, 7, pp.6473~ (2017)
- Zellweger JP, "Risk assessment of tuberculosis in contacts by IFN-γ release assays. A Tuberculosis Network European Trials group study", Am J Respir Crit Care Med, 191, pp.1176~1184 (2015)
- Arend SM, "Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides", Infect Immun, 68, pp.3314~3321 (2000)
- Mahnke YD, "Age-related changes in durability and function of vaccine-elicited influenza-specific CD4(+)T-cell responses", Vaccine, 29, pp.8606~8614 (2011)