Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-[gamma], IP-10 and adenosine deaminase

• Published in: PloS one 2018-08, Vol.13 (8), p.e0202481
• Main Authors: Santos, Ana Paula, Corrêa, Raquel da Silva, Ribeiro-Alves, Marcelo, Soares da Silva, Ana Carolina Oliveira, Mafort, Thiago Thomaz, Leung, Janaína, Pereira, Geraldo Moura Batista, Rodrigues, Luciana Silva, Rufino, Rogério
• Format: Article
• Language: English
• Subjects: Adenosine deaminase; Diagnosis; Health aspects; Interferon; Pleural diseases; Testing; Tuberculosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202481

Pleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-[gamma]), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases. Eighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-[gamma] release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-[gamma] and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-[gamma] and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-[gamma] showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-[gamma] plus ADA .sub.(cut-point: 25.80 IU/L) represent the most accurate biomarker comb