Enzymes of purine metabolism — biomarkers for the diagnostics of tuberculous pleurisy in patients with HIV infection

The objective of the study was to evaluate the information content of determining the activity of adenosine deaminase and adenosine deaminase-2 in the diagnosis of tuberculous pleurisy in patients with HIV infection.

Materials and methods. A total of 378 patients with pleural effusion were retrospectively examined. In 215 cases, tuberculous pleurisy was detected (TP); and 163 patients had non-tuberculous pleural effusion (non-TP). As much as 27 patients in the TP group were HIV co-infected (TP/HIV+), the remaining 188 patients were HIV — negative (TP/HIV–). In all the patients, the activity of total adenosine deaminase (ADA) and its isoenzymes (ADA-1 and ADA-2) in the pleural fluid was determined.

Results and discussion. In the TP group, the activity of total ADA (95.5 [67.7; 115.4] versus 82.0 [59.6; 100.0] U/L, p=0.1), ADA-1 (14.2 [5.8; 20.5] versus 12.1 [6.1; 23.7] U/L, p=0.9) and ADA-2 (78,1 [38.1; 93.1] versus 62.4 [35.4; 82.2] U/L, p=0,1) did not depend on HIV status. The activity of these indicators was determined above the threshold level — total ADA in 96.3% and 95.2%, ADA-1 in 25.9% and 30.8% and ADA-2 in 92.6% and 83.3% of cases in the «TP/HIV+» and «TP/HIV–» groups, respectively. A negative correlation between ADA-1 activity and HIV viral load in the group of patients with tuberculous pleurisy and HIV infection (r=–0.45; p=0.008), as well as in the subgroup of TP/HIV+ patients who received (r=–0.9; p=0.008) and in those who didn’t receive ART (r=–0.47; p=0.04) was obtained. Our results show that a total ADA activity increase in the patients with tuberculous pleurisy, regardless of patients’ HIV status, occur due to ADA-2. Thus, the increase in activity of total ADA and ADA-2 in our study was caused by active tuberculosis, not by the presence or absence of HIV co-infection. Also, the ADA-2 activity in HIV-infected patients is likely consistent with ADA-2 important role in cellular immune responses.

Conclusion. Our data indicate the participation of purine metabolism enzymes in the pathogenesis of HIV infection. At the same time, adenosine deaminase activity is not a specific biomarker of individual changes characteristic of HIV infection. The study results suggest that the total adenosine deaminase and adenosine deaminase-2 activity increase is a valuable and diagnostically significant marker of tuberculous pleurisy in HIV-infected patients. The value of adenosine deaminase and adenosine deaminase-2 activity remains high even in the patients having severe immunosuppression, which allows them to be actively used for rapid diagnostics and hence, early TB therapy initiation.

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