The increased production level of 15 cytokines associated with tuberculosis severity and patients’ responsiveness to therapy

Pulmonary tuberculosis (TB) is clinically heterogeneous disease that may develop as a result of immune deficiency or immune hyperreactivity. Exact factors and markers associated with both types of immune dysfunction are not fully clear. To analyze the heterogeneity of immune reactivity of TB patients, we have analyzed the levels of 47 cytokines in the serum and antigen-induced plasma (AG-plasma) of TB patients and their associations with TB severity and responsiveness to TB treatment. Serum and AG-plasma were obtained from 37 patients with recently-diagnosed TB; cytokines were evaluated using xMAP multiplex assay. TB severity and patient’s responsiveness to treatment were assessed based on microbiological, radiological and clinical data at admitting and after 2 months of therapy. Statistical analysis was performed in R-studio using non-parametric correlation and hierarchical clustering analysis. In hierarchical clustering analysis, 15 out of 47 cytokines divided all patients into high-producers and low-producers. High-producers had more severe TB, i.e., a higher rate of bacterial excretion (80% versus 27% in low-producers’ group) and pulmonary destruction (65% versus 47%). High-producers also showed poorer response to TB therapy. The cytokines that clustered patients into two groups included type I interferons, factors associated with neutrophil response, and IL-10 superfamily members involved in inflammatory reactions. The results contribute to better understanding of TB pathogenesis and identify immune markers may help detecting patients with severe TB and poor prognosis for whom personalized immunotherapy may be beneficial. Supported by Grant RSF17-75-10197