TY - JOUR
T1 - Diagnostic Accuracy of Interferon Gamma-Induced Protein 10 mRNA Release Assay for Tuberculosis
AU - Blauenfeldt, Thomas
AU - Villar-Hernandez, Raquel
AU - García-García, Esther
AU - Latorre, Irene
AU - Holm, Line Lindebo
AU - Muriel-Moreno, Beatriz
AU - De Souza-Galvão, Maria Luiza
AU - Millet, Joan Pau
AU - Sabriá, Fina
AU - Sánchez-Montalva, Adrián
AU - Ruiz-Manzano, Juan
AU - Pilarte, Jose
AU - Jiménez, María A
AU - Centeno, Carmen
AU - Torres, Carmen
AU - Molina-Pinargote, Israel
AU - González-Díaz, Yoel D
AU - Santiago, Javier
AU - Cantos, Adela
AU - Prat, Cristina
AU - Andersen, Peter
AU - Dominguez, Jose
AU - Ruhwald, Morten
N1 - Copyright © 2020 American Society for Microbiology.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.
AB - Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.
KW - IP-10
KW - diagnosis
KW - mRNA
KW - qPCR
KW - tuberculosis
KW - Tuberculosis
KW - QPCR
KW - Diagnosis
UR - http://www.scopus.com/inward/record.url?scp=85091585963&partnerID=8YFLogxK
U2 - 10.1128/JCM.00848-20
DO - 10.1128/JCM.00848-20
M3 - Journal article
C2 - 32719030
SN - 0095-1137
VL - 58
JO - Journal of Clinical Microbiology
JF - Journal of Clinical Microbiology
IS - 10
M1 - e0084820
ER -