Mikhail F. Ivanov

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is a natural focal viral infection with a high probability of severe course, the possibility of death, a long recovery period after infection, low effectiveness of therapy and vaccine prevention. In the Russian Federation, HFRS is most often caused by the Puumala orthohantavirus. The aim of the study — to evaluate the immunophenotypic composition of lymphocytes and cytokine profile in the blood of patients with hemorrhagic feverwith renal syndrome in comparison with acute respiratory viral infections and with the prospect of developing immunological criteria for early diagnosis of HFRS. Matherials and Methods. There were examined the blood of 24 patients with a verified diagnosis of HFRS who were hospitalized in the infectious diseases department of the Samara Medical University Clinics and admitted in the first days of the disease, 18 patients with acute respiratory viral infections of established etiology, as well as 15 healthy people. Results and Discussion. Analysis of the results of lymphocyte phenotyping and cytokine levels in the blood revealed that the percentage of B lymphocytes in the blood was 12.6 %, cytotoxic CD8+ T lymphocytes expressing the activating lectin receptor NKG2D (CD3+CD8+CD314+), 25 %, regulatory T cells with CD3+CD4+FoxP3+ phenotypes 7.8 % and CD3+CD8+FoxP3+ 9.5 %, as well as IL-6 24 pg/ml, TNFß 55 pg/ml, IL-10 11.3 pg/ml with high diagnostic significance, judging by the results of ROC analysis, indicates in favor of GLPS, but not ARVI. Conclusion. The results obtained can be used as criteria for early immunodiagnosis of HFRS. The development of a new hypothesis on the mechanism of CD8+ immunological memory formation may contribute to the discovery of new potential targets for HFRS immunotherapy and the creation of new principles for the production of vaccine preparations for the prevention of this disease.

Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focal disease of a viral nature. Its severity is determined by hemorrhagic phenomena, cytokine storm, kidney damage with the development of acute renal failure, and the possibility of death. HFRS is caused by viruses from the family Hantaviridae. Hantaviruses are characterized by the ability to infect endothelial and epithelial cells of the renal tubules, as well as innate immunity cells (neutrophils, monocytes, dendritic cells), which leads to both direct damage to the immune system and indirect through a violation of their functions. The review analyzes the immune mechanisms in HFRS and their role in the pathogenesis of this disease.

Aim to evaluate the pathogenetic role of T-lymphocytes carrying the natural killer marker CD56 in hemorrhagic fever with renal syndrome (HFRS). Material and methods. The study group included 65 patients with HFRS receiving the inpatient treatment in the Clinics of SamSMU, and 15 healthy people were chosen for the control group. The following examinations were scheduled for all patients in the different stages of the disease: a clinical blood test, flow cytometry with a given set of monoclonal antibodies, enzyme-linked immunosorbent assay of blood serum to determine the cytokine profile. For statistical analysis we used the SPSS v.23 software. Results. The percentage of CD3+ CD56+ NKT blood content in comparison with those for cells of innate immunity (neutrophil granulocytes, monocytes, natural killers) and lymphocytes of adaptive immune response, as well as the level of cytokines in the blood serum showed that in polyuric and convalescent periods, the number of these cells significantly increases and remains closely embedded in correlations with other components of the immune system. Conclusion. A new hypothesis has been proposed to interpret the role of NKT in the development of the immune response in HFRS.

The aim of the work is to determine the relationship between the levels of cytokines of proinflammatory and anti-inflammatory action during the clinical course of hemorrhagic fever with renal syndrome (HFRS) and the previously described characteristics of the phenotypic composition of blood lymphocytes in disease of various severity. Materials and methods. 65 patients with a serologically verified diagnosis of HFRS were under observation. The control group included 15 conditionally healthy people. Determination of cytokines in the blood of patients with HFRS was carried out by the enzyme immunoassay method at the different stages of the disease. The phenotypic composition of blood lymphocytes was assessed by flow cytofluorimetry. Results. At the different stages of the disease, there was a quantitatively different increase in the content of cytokines in the blood associated with cytotoxic immune reactions (IL-12, IFN, TNFa, TNF), as well as IL-10 and IL-6 correlated with each other in severe cases, against the background of a drop in blood levels of IL-4 and IL-1. In the moderate course of HFRS, correlations of IL-12 and IL-4 with NKG2D+ CTL, the relationship of IL-12 with almost all other cytokines, and the correlation of CD8+ Treg with IL-6 and TNF levels were observed. In severe cases, the formation of a complex that included interconnected IL-6 and IL-10 correlating with the number of NKG2D+ CTL, CD8+ Treg, NKT was noted. Conclusion. The pathogenetically significant mechanism of HFRS is realized with the predominant participation of cytokines of the cellular immune response and IL-6, correlatively associated with NKG2D+ CTL, CD8+ Treg, NKT, which, in case of a favorable outcome, contribute to the active formation of a pool of CD8+ memory cells, disrupted presumably by excessive secretion of IL-10.

The study is devoted to the assessment of the role of immune mechanisms in the development of acute renal failure in HFRS. The material for the study was the blood of 65 patients with HFRS and 17 patients with ALF of toxic nature from the comparison group as models of kidney damage by hantavirus and non-infectious genesis and 15 clinically healthy subjects of the control group. Data were obtained that allow us to consider the cytolytic effects of natural killer cells and cytotoxic T-lymphocytes activated by the NKG2D-dependent method as damage factors, including renal tissue, and a significant increase in the content of regulatory T-cells in the blood as protective mechanisms.

Прогностическое значение фенотипических изменений лимфоцитов при геморрагической лихорадке с почечным синдромом

Экспрессия NKG2D цитотоксическими Т-лимфоцитами как возможный механизм иммунопатогенеза геморрагической лихорадки с почечным синдромом