Enzymes of purine metabolism and lymphocyte subpopulations in patients with drug-sensitive and drug-resistant infiltrative pulmonary tuberculosis

The purpose of our study was to evaluate the enzyme profile of purinergic system and lymphocyte subsets in patients with newly diagnosed infiltrative pulmonary tuberculosis (IPT), depending on the drug resistance of Mycobacterium tuberculosis ( Mtb) to anti-tuberculosis drugs. In 109 patients with drug-sensitive Mtb (significant or less pronounced improvement after intensive phase of chemotherapy), or in drug-resistant cases, the activity of adenosine deaminase (eADA-1, 2), concentration of ecto-5’-nucleotidase (eNT5E), CD26 (DPPIV), and the composition of lymphocyte subsets were evaluated before treatment. The IPT patients with drug-sensitive Mtb strains who achieved a “less pronounced improvement” exhibited higher concentrations and activity of ectoenzymes responsible for production of extracellular adenosine (eNT5E) and its transformation (eADA-1 and eADA-2). The proportion of cytotoxic T cells was also higher compared with patients who achieved significant improvement. Patients isolating drug-resistant Mtb strains who achieved a “less pronounced improvement” had lower absolute counts of T lymphocytes and helper T cells with an increased proportion of cytotoxic T cells and elevated eADA-2 activity compared with individuals who achieved significant improvement. Thus, prior to initiation of tuberculosis chemotherapy, the activity of purine metabolism enzymes and the subpopulation profile of lymphocytes were not associated with the characteristics of Mtb drug resistance. A relationship between the parameters of purinergic regulation enzymes and numbers/ ratio of lymphocytes was revealed in patients who achieved significant improvement. Such relationships were not revealed in the group with less pronounced improvement, regardless of the drug resistance of Mtb . These findings suggest an imbalance of inflammatory factors and immune response to Mtb in the patients who showed worse clinical outcomes after intensive chemotherapy. Taking into consideration each component of protective reactions is required for administration of adequate chemotherapy, pathogenetic treatment, and immunocorrective treatment in order to prevent progression of the disease.