Apolipoprotein A-I (ApoA-I) is the main functional protein component of human high-density lipoproteins. ApoA-I shows various anti-inflammatory and atheroprotective properties toward macrophages; however, endogenous apoA-I expression has not been investigated in macrophages. We have shown that endogenous apoA-I gene is expressed in human macrophages at both mRNA and protein levels. Endogenous ApoA-I is localized in intracellular vesicles and at the external side of the plasma membrane in association with ATP-binding cassette transporter A1 (ABCA1) and lipid rafts in macrophages. We have shown that endogenous ApoA-I stabilizes ABCA1, moreover, down-regulation of ApoA-I by siRNA results in an increase of Toll-like receptor 4 (TLR4) mRNA and membrane surface protein expression, as well as an enhancement of bacterial lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and inducible nitric oxide synthase (NOS2) genes in human macrophages. TNF-α stimulates ApoA-I expression and secretion (1.2±0.2 vs. 4.3±0.9 ng/mg total protein) in macrophages. Obtained results suggest that endogenous ApoA-I has anti-inflammatory properties, presumably due to ABCA1 stabilization in macrophages; these results elucidate the cell type-specific mechanism of the TNF-α-mediated regulation of apoA-I gene expression in monocytes and macrophages.

Despite the great interest of the scientific community in the behavior of the human body after contact with the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), long‐term (more than 6 months) monitoring of the immunological status of patients with coronavirus disease 2019 (COVID‐19) having varying severity degrees and of the people with a low SARS‐CoV‐2 viral load is practically absent. The aim of this study is a 9‐month monitoring of SARS‐CoV‐2 infection immune response development and extinction using quantitative assessment of IgA and IgG levels in the blood of healthy donors living in the context of the coronavirus pandemic and of the patients who have undergone COVID‐19. The project involved 180 volunteers, of whom 51 persons (28.33%) fell ill with COVID‐19 during the observation period. All people who underwent COVID‐19 developed a stable humoral immune response but their individual immune status had a number of features. Approximately 39.22% (20 of 51 people) of project participants diagnosed with COVID‐19 showed an unusual change in plasma anti‐SARS‐CoV‐2 IgA levels. Relatively high levels of IgA (ratio ~ 3) after recovery persisted for a long time (more than 6 months). In one‐third (17 of 51 people) of patients with COVID‐19, the IgA level exceeded the IgG level. IgA antibodies appeared earlier and showed a stronger and more robust response to the SARS‐CoV‐2 virus than IgG. Increased levels of anti‐SARS‐CoV‐2 IgA (ratio from 0.8 to 2.36) throughout the observation period were recorded in 28 of 180 project participants (15.56%) of whom only one person fell ill with COVID‐19.

Background: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP. Materials and methods: During 2009-2015 in the University Hospital of St. Petersburg State University, blood samples were analyzed from 550 women with different reproductive system disorders preparing for IVF and 46 healthy women in control group. In total, 28 SNP were analyzed in the genes of thrombophilia factors, folic acid cycle, detoxification system, and the renin-angiotensin system. The method used was real-time PCR. Results: A significant increase in the frequency of pathological alleles of some polymorphisms in patients with habitual failure of IVF was shown, compared with the control group. As a result, two options defined panels for optimal typing SNP before IVF were composed. Standard panel includes 8 SNP, 5 in thromborhilic factors, and 3 in folic acid cycle genes. They are 20210 G4A of FII gene, R506Q G4A of FV gene (mutation Leiden), -675 5G44G of PAI-I gene, L33P T4C of ITGB3 gene, -455 G4A of FGB gene, 667 C4T of MTHFR gene, 2756 A4G of MTR gene, and 66 A4G of MTRR gene. Extended panel of 15 SNP also includes 807 C4T of ITGA2 gene, T154M C4T of GP1BA gene, second polymorphism 1298 A4C in MTHFR gene, polymorphisms of the renin-angiotensin gene AGT M235T T4C and -1166 A4C of AGTR1 gene, polymorphisms I105V A4G and A114V C4T of detoxification system gene GSTP. Conclusion:The results of SNP genotyping can be adjusted for treatment tactics and IVF, and also medical support getting pregnant. The success rate of IVF is increased as the result, especially in the group with the usual failure of IVF.

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At the present time, studying humoral immunity to the new coronavirus infection is among the most important tasks. The COVID-19 infection induces a protective pool of specific antibodies determining severity and duration of such immune protection after convalescence. The antibody testing is also necessary for assessing efficiency of anti-COVID vaccines in order to defeat the SARS-CoV-2 pandemic. Despite enormous interest of scientific community in this problem seen in the literature, there is still a lack for longitudinal observations of immunological status (more than 6 months) in the patients who have undergone COVID-19. The aim of this study is a long-term monitoring (9-14 months) of development and extinction of immune response to SARS-CoV-2 infection using quantitative assessment of IgA and IgG levels in peripheral blood of the patients who had COVID-19 in anamnesis. Monitoring of anti-SARS-CoV-2 levels over time has demonstrated significant individual variability, and made it possible to divide the study participants into three groups, according to characteristic features of humoral immunity after documented COVID-19. The study describes characteristic features of humoral immune response for each of these groups. The first group (30% of the study group) exhibited classical pattern of antibody response to viral infection. The second group (40% of study participants) presented with high plasma IgA levels, and their significant excess (about 2 times) over IgG levels throughout the observation period. The third group (30% of study participants), apparently comprised the subjects with increased humoral immunity to SARS-CoV-2 infection. Their plasma antibodies remain at high levels for at least 9-10 months after the onset of infection. The data obtained confirm the pattern of plasma IgA which is not quite typical to viral infections in dynamics after a sufficiently long time period after the disease in most study participants (2nd and 3rd groups; 70% of all volunteers who have recovered from COVID-19) and suggests an important role of this immunoglobulin against SARS-CoV-2 infection. The specific responses of anti-SARS-CoV-2 IgG are very similar to behavior of such antibodies in other viral infections including contacts with coronaviruses from earlier generations. Humoral immunity against SARS-CoV-2 may persist for more than 6 months, thus supporting an assumption that the naturally infected patients are able to resist re-infection for a long time.