BACKGROUND: Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancer patients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid. METHODS: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio. RESULTS: Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry. CONCLUSIONS: These results suggest that IDO is strongly involved in the pathogenesis of TBP.
BACKGROUND: Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancerpatients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid. METHODS: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio. RESULTS: Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry. CONCLUSIONS: These results suggest that IDO is strongly involved in the pathogenesis of TBP.
Authors: Jeffrey M Collins; Amnah Siddiqa; Dean P Jones; Ken Liu; Russell R Kempker; Azhar Nizam; N Sarita Shah; Nazir Ismail; Samuel G Ouma; Nestani Tukvadze; Shuzhao Li; Cheryl L Day; Jyothi Rengarajan; James Cm Brust; Neel R Gandhi; Joel D Ernst; Henry M Blumberg; Thomas R Ziegler Journal: JCI Insight Date: 2020-05-21
Authors: Uma S Gautam; Taylor W Foreman; Allison N Bucsan; Ashley V Veatch; Xavier Alvarez; Toidi Adekambi; Nadia A Golden; Kaylee M Gentry; Lara A Doyle-Meyers; Kasi E Russell-Lodrigue; Peter J Didier; James L Blanchard; K Gus Kousoulas; Andrew A Lackner; Daniel Kalman; Jyothi Rengarajan; Shabaana A Khader; Deepak Kaushal; Smriti Mehra Journal: Proc Natl Acad Sci U S A Date: 2017-12-18 Impact factor: 11.205
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Authors: James J Phelan; Sharee A Basdeo; Simone C Tazoll; Sadhbh McGivern; Judit R Saborido; Joseph Keane Journal: Front Immunol Date: 2018-10-15 Impact factor: 7.561