Analysis of changes in matrix metalloproteinases-9 and tissue inhibitors-1 levels in newly diagnosed pulmonary tuberculous with different profile of drug-resistance
Authors: Shevchenko О.S. , Todoriko L.D. , Ovcharenko I.A. , Pohorielova O.O. , Shvets O.M. 
Published: September 2022

Objective — to analyze changes in MMP-9 and TIMP-1 parameters in patients with newly diagnosed destructive pulmonary TB with different pathogen resistance profile depending on the course of the tuberculosis process.

Materials and methods. The study included 124 patients with newly diagnosed pulmonary TB with destruction and bacterial excretion, who were treated according to the order of the Ministry of Health of Ukraine N 620 in 2014—2017. The patients were divided into 2 groups: Group I (n = 84) — multidrug-resistant TB (MDR-TB); Group II (n = 40) — drug-susceptible TB. Groups Ia (n = 56) and IIa (n = 28) included patients with effective treatment; groups Ib (n = 28) and IIb (n = 12) included patients with ineffective treatment. The level of MMP-9 and TIMP-1 was studied in blood serum by ELISA. Blood was taken in the morning on an empty stomach at the beginning of treatment, after 2 and 3 months.

Results and discussion. The level of MMP-9 increased in both groups for 3 months. However, the dynamics of the increase was more intensive in the group of drug-susceptible TB. The level of TIMP-1 also increased within 3 months in both groups. This dynamics was more intensive in Group II. In the course of treatment, more intensive dynamics of the ratio decrease MMP-9/TMP-1 was observed in Group II with a decrease of 25 % compared with 16.6 % in Group I.In the group of patients with MDR-TB, the ratio of MMP-9/TIMP-1 at the beginning of treatment was lower in Group Ia than in Group Ib (p < 0.001). Its decrease within 3 months was more pronounced in Group Ib (by 25 %) compared with Group Ia (7.5 %). In the group of patients with drug-susceptible tuberculosis at the beginning of treatment, higher levels of the MMP-9/TIMP-1 ratio were observed in Group IIb. Against the background of anti-TB treatment for 3 months. There was also a decrease in the ratio in both groups (IIa and IIb). However, the dynamics of the decrease was more pronounced in Group IIb (by 41 %), compared with group IIa (by 10 %).

Conclusions. In dynamics, against the background of antimycobacterial therapy, a more rapid onset of lung healing processes was observed in patients with drug-susceptible pulmonary TB compared with patients with MDR-TB. This is evidenced by the obtained indicators of MMP-9, TIMP-1 and their ratio. Thus, the level of TIMP-1, which is an inhibitor of MMP-9, was higher after 3 months of treatment and showed more intensive growth dynamics in Group II, that is, in patients with drug-susceptible TB, which indicates a favorable course of the disease in this group, and an earlier onset of healing processes of lung tissue destruction.When patients were divided into groups of effective and ineffective treatment, a more intensive decrease in the ratio of MMP-9 to TIMP-1 was observed in patients with an unfavorable course of the tuberculosis process, which indicates more significant changes in the connective tissue of the lungs in patients from these groups.