Liadova T. Role of immune, autoimmune and genetic disorders in pathogenesis, clinical manifestations and consequences of EBV-infection and methods of its correction

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0518U000578

Applicant for

Specialization

  • 14.03.08 - Імунологія та алергологія

15-05-2018

Specialized Academic Board

Д 64.618.01

State Institution "I.Mechnikov Institute of Microbiology and Immunology National Academy of Medical Sciences of Ukraine"

Essay

Object of research: infectious mononucleosis, chronic EBV-infection. The aim of the study: improving the treatment effectiveness, predicting the course and prevention of the effects of EBV-infection on the basis of the study of molecular genetic mechanisms and immune disorders. Research method: general clinical, immunological, biochemical, immuno-enzymatic, molecular-genetic, and statistical. Equipment: amplifier BIS; FACS-Calibur (USA); immuno-enzyme analyzer Personal Lab. Theoretical and practical results. Novelty. Based on the results of the genotyping of the DNA of the EBV in the Kharkiv region, the prevalence of the EBV-1 genotype was found in both groups of patients with IM and in the case of CEBV-infection. For the first time a comprehensive description of immune disorders, pro- and anti-inflammatory cytokines, autoimmune, genetic markers in the pathogenesis of the disease has been provided and their role as predictors of the course and consequences of EBV-infection has been established. Immune parameters, types of cytokine response, genetic markers that promote the transition of IM to a past-infection and associated development of chronic infections are determined. The immune status of patients with CEBV-infection was investigated, the character of violations in the cellular, humoral and phagocytic links of the immune system was determined. For the first time four types of cytokine response for EBV-infection were established: normoreactive, dissociative, hyporeactive and hyperactive, on the basis of which the course and form of the disease are predicted. For the first time at the EBV-infection, the definition of the 1486 T/C TLR-9 gene was determined, which made it possible to find out that the presence in the genome of patients with the IM genotype of the CC is specific for patients with IM. When detecting the homozygous allele of the CC -1486 T/C TLR-9 gene, the probability of the dissociative type of response is predictable, which is associated with a torpid course of the disease and reconvalescence and the development of possible complications. In the case of CEBV, the prevalence of selected genotypes revealed a dominance of the TC genotype, compared with the genotypes of TT and CC. Research of the nature of correlations and structures in the period of the height of the IM revealed the intensity of the immune system by the type of hypercompensation (CLI/CLE=1,49), with CVEB in the period of reactivation, marked pronounced disproportion (CLI/CLE=0,65) was noted, indicating about the presence of the immune system in the crisis mode of functioning with the phenomena of exhaustion. The efficacy of a drug containing aloferone 1 mg (alokine alpha) and recombinant interferon-α2β (viferon) in complex correction of immune disorders in patients with chronic forms of EBV-infection is proved, which has a significant positive effect on the dynamics of the main clinical symptoms, immunograms and the cytokine profile. Degree of implementation. 12 acts of implementation, 3 patents. Branch (industry) of use: health (medicine: immunology, infectious diseases).

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