Project objective: evaluate the role of regulatory T-lymphocytes in the immunopathogenesis and in the development of adverse clinical outcomes in patients with brucellosis considering inclusion in complex treatment of the immunomodulator.
Current status of the research. It is known that the frequency of relapses in patients with brucellosis reaches 20%.
At the same time, there is evidence of the crucial role of violations of the T-cell immunity in the development of relapses and chronic brucellosis. In the available literature, we found only reference to the study of regulatory T-lymphocytes in humans with acute and chronic brucellosis (Bahador A., Hadjati J., Hassannejad N., Ghazanfari H. et al., 2014). The authors found an association between the development of brucellosis in humans, and an increase in CD4+Treg cells and their CD25high and FoxP3high fractions. However, the impact on them of the treatment was not taken into consideration. Thus, it is interesting to trace the dynamics of regulatory T-lymphocytes in connection with antibiotic therapy and pharmacological immunomodulation.
The impact of the project at the developing area: New data on the background changes in the immune status in patients with brucellosis, as well as the dynamics of T-regulatory lymphocytes under the influence of different modes of therapy will help to significantly improve understanding of the mechanisms of the parasite - host interaction at brucellosis and the development of resistance to the in vivo treatment of this infection. The practical importance of the tasks of carried out research is the possibilities to influence the studied pathophysiological mechanisms and significantly improve the prognosis for patients with brucellosis both in reducing the number of relapses, and the elimination of the pathogen.
The participants of the proposed project have extensive experience in the study of various aspects of immunology of recurrent bacterial infections, including brucellosis, as well as approaches to the treatment of this infection.
Expected results and their use. Determination of laboratory markers of clinical efficacy of the brucellosis treatment, predictors of chronicity and relapse. Assessing the impact of the WHO-recommended regime of the brucellosis etiotropic treatment (doxycycline + cyprofloxacin) on the microbiological, immunological, clinical signs of infection, including the dynamics of regulatory T-lymphocytes, development of relapses and the elimination of Brucella. Justification of the feasibility of immunomodulation in the treatment of brucellosis and the selection of its optimal scheme. The data obtained will be both fundamental and applied nature in terms of development of predictive schemes of the treatment effectiveness and the development of clinical protocols of the pathogenetically justified treatment of various forms of brucellosis. Accumulated database will be made available not only for the project participants, but also for those, who interested in the scientific community.
Compliance of the Project with the objectives of ISTC. Since the project will involve specialists previously associated with the production of biological weapons, for the realization of peace studies, he meets the ISTC goals and tasks.
The role of foreign collaborators: Leading Professor of Microbiology and Immunology, University of Texas, an expert on especially dangerous infections will be a consultant in the implementation of planning and carrying out the clinical material researches, as well as in the interpretation of laboratory results. The collaborator will monitor the results of research throughout the project period. The collaborator will evaluate the possibility of continued cooperation after the end of the project.
Technical Approach and Methodology:
We will carry out a prospective observation of patients with clinical symptoms, not excludede brucellosis. The study will include patients with serologically confirmed brucellosis (both acute and chronic forms in the acute phase), with subsequent verification of the diagnosis by genetic and bacteriological methods. It is planned to investigate at least 80 patients with brucellosis. Subsequently, the contingent will be divided randomly into groups (in compliance with the principles of representative samples) to study the elimination of Brucella, as well as evaluating the clinical efficacy of the immunomodulator, Polyoxidonium, for outcomes of brucellosis. With the use of monoclonal antibodies in each patient will be evaluated absolute number of lymphocytes and different subpopulations of T-lymphocytes based on expression of the molecules CD4, CD25, Foxp3 markers of their functional activity before treatment and on day 10 after treatment.
