V.V. Novitsky
O.I. Urazova
O.V. Voronkova
I.O. Naslednikova
T.A. Shilko
R.R. Hasanova
V.A. Serebryakova
T.E. Budkina
Ju.V. Stambula
A.E. Kolosova
T.V. Fedorovich
M.G. Skorohodova
E.N. Chernova |
THE MOLECULAR-GENETIC BASES OF MANAGEMENT OF HUMAN
ADAPTABLE BLOOD SYSTEM REACTIVITY DURING INFECTION |
| Siberian State Medical University, Tomsk, Russia |
The aim of research: on the basis of fundamental knowledge about molecular-genetic
mechanisms of immunocompetent blood cells homeostasis disregulation to offer
a theoretical substantiation of methodology of management of human adaptable
anti-infectious protection system during socially-significant virus and
bacterial infections. During performance of research, features of disregulation
of spontaneous and induced production of IL-1,-2,-3,-4,-5,-10,-12, TNF-, IFN-,
TGF-, GM-CSF, blood cells proliferation and differentiations are established
during virus infections (a virus hepatites B, C, herpetic, Epstein-Barr-virus
infection) and bacterial infection (a pulmonary tuberculosis). The mechanisms
of cytokine-mediated blood leukocytes cooperation infringements during infections
was determinate, the polymorphic variants of genes IL-1RN, +3953 A1/A2 IL-1,
T-330G IL-2, C-590T IL-4, C-592A IL-10, A1188C IL-12, G308A TNF-α prevalence
was estimated, the interrelation between cytokine genes polymorphism and parameters
of clinical course and immunocompetent blood cells adaptive reactivity in healthy
Russian aboriginal and in patients with virus hepatites B, C, herpetic, Epstein-Barr-virus
infection and tuberculosis was analysed. The genetic polymorphism of HCV and
M. tuberculosis infecting strains was analyzed. The interrelation between genotypical
structure of M. tuberculosis infecting strains and parameters of a clinico-radiological
picture of multidrug resistant pulmonary tuberculosis, features of diseases
course and dynamics of pathognomonic attributes changes on a specific
therapy background was established. The data about association of immunodeficiency
character with genetically determined disbalance of the basic immunoregulatory
cytokines secretion, supervising proliferation and a differentiation of blood
cells, generate a theoretical basis of the methodological approach to correction
of immunocompetent blood cells adaptive reactivity during infection diseases.
The revealed deficiency of basic proinflammatory cytokines production
during virus hepatites B, C, herpetic, Epstein-Barr-virus infection and tuberculosis
can be levelled by immunomodulating drugs like recombinant cytokines by replaceable
therapy principle, that will allow to normalize simultaneously production and
receptors expression of anti-inflammatory interleukins, considering a
principle of autocrine and paracrine regulation of cytokines secretion. Such
approach to immunocorrection will allow to correct at the certain stage process
of Т-helper dichotomy and to avoid polarization of the immune response
in direction Th2, and, consequently, to generate the protective cell-mediated
type of immune response for under study infections. Established during pulmonary
tuberculosis association between cytokines genes polymorphism (allele А2
of polymorphism +3953А1/А2 of gene IL1RN and a genotype С/С
of polymorphic site 1188А/С of gene IL12B) with a level of corresponding
proteins production allow to recommend a method of immunogenetic testings for
forecasting immunopathological complications, for duly prevention and the personalized
correction. As demonstrated research results, special indications for such immunocorrigent
therapies can be: in patients with pulmonary tuberculosis - multidrug resistance,
and M. tuberculosis transmission activity which can be detected by MIRU- genetic
typing; in patients with a virus hepatites B, C - «not 1b» HCV type.
