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The main histocompatibility complex — HLA system (Human Leukocyte Antigens) is among the most important genetic factors determining response of humans to infectious agents. The key role that HLA molecules play in immune response is to present the pathogen-derived peptides. Enormous molecular variability of HLA alleles in human populations have attracted close attention and became the basis for numerous studies aimed at evaluating the role of HLA genotypes for individual features of immune response to COVID-19, the new infection caused by SARS-CoV-2 β-coronavirus. Many studies have focused on search of specific alleles associated with both susceptibility and resistance to this disease. Separate HLA patterns were reported already. These patterns may be either universal to several populations, or rather peculiar, since distribution of HLA genes is different for various populations, depending on the living conditions, including specific protection from environmental pathogens. Therefore, it is evident that individual effects of HLA genotype upon occurrence and course of SARS-CoV-2 infection should be performed in comparison with the HLA distribution among the residents of appropriate region. The objective of this study was to compare the distribution of HLA-A*, B*, DRB1* allele groups, and to analyze the frequencies of HLA-AB-DRB1 haplotypes in subjects with COVID-19 (n = 138), compared with the control group presented by residents of the North-Western Russia (n = 1456). The most significant differences between COVID-19 patients compared with a group from control population were revealed for the groups of HLA-A* alleles: the frequencies of HLA-A*02 and HLA-A*26 were significantly reduced (39.86% versus 51.72%, χ2 = 7,58, and 4.35% versus 9.07%, χ2 = 4.17, respectively). At the same time, the frequency of HLA-A*29 was increased more than 2-fold (5.80% versus 2.47%, χ2 = 4.03). This finding suggests that the allele groups A*02 and A*26 are associated with reduced likelihood of the disease, while A*29, is an apparent factor predisposing for susceptibility to the disease. It was found that occurrence of definite HLA haplotypes, including the A*02 allele group, is less common in persons who have undergone COVID-19, and are ranged at the 4th, 7th and 10th positions in frequency, while in the population control group such HLA haplotypes took the 3rd, 4th, 7th and 8th places. Further evaluation of the HLA gene polymorphism will allow to understand the predetermined immunogenetic basis for susceptibility, as well as clinical severity of COVID-19.

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%.

Abstract. Present study defines clinical, hormonal and immunological factors allowing to predict outcomes of IVF cycles in patients with combined forms of infertility at their reproductive age. Indices of gonadotrophic ovarian stimulation in IVF cycles in patients of reproductive age with combined forms of infertility depend on their age and cytokine contents in follicular fluid. Effectiveness of gonadotropin-induced ovarian stimulation is inversely dependent on the patients’ age, its increase is related to increased contents of pro-inflammatory cytokines in follicular fluid and increased expression of CCR1, along with decreased expression of CCR3 chemokine receptors in endometrium. Effectiveness of gonadotropin-induced ovarian stimulation depends on concentration of cytokines in the follicular fluid, which is argued by presence of a significant direct correlation between the number of growing follicles, oocytes and local contents of IL-10, IL-15, eotaxin, MIP-1β, RANTES, TNFα, IFNγ, and GMCSF. Free testosterone levels show a positive correlation with numbers of oocytes obtained from the ovarian punctate, and CXCR2 and CCR3 expression in endometrium, as well as a negative correlation was found with IL-4 contents in follicular fluid. In patients with negative IVF cycle outcomes, levels of IL-13 in follicular fluid upon ovarian stimulation proved to be twofold higher than those in patients with successful pregnancy after IVF. Prognosis for pregnancy in a cycle of treatment in patients with combined forms of infertility of reproductive age is determined by a patients’ story, and a variety of clinical, hormonal and embryological factors which can increase predictive accuracy of the IVF outcomes. To determine a probability of successful pregnancy after IVF cycle, an appropriate prognostic index is recommended, with a sensitivity levels of 93% and specificity of 89%.