Russian Journal of Infection and Immunity

Abstract. The objective of this review was to highlight the problem of sepsis, the relevance of which is determined by the growing number of patients, the complexity of pathogenesis, and the difficulty of early diagnosis. Sepsis is a life-threatening severe dysfunction of internal organs caused by an infectious agent and occurring as a result of a complex interplay between proinflammatory and anti-inflammatory processes that can lead to multiple organ failure and death. This condition holds one of the leading places in morbidity and high mortality in surgical and intensive care units, and its prevalence has continued to steadily increase over the past years, especially among groups of patients with chronic diseases and weakened immunity. At different stages of pathogenesis, immune mechanisms act as both a generator of damage reactions and the main components of the body’s defense reactions. Sepsis begins with an exuberant inflammatory reaction, which can last for several days, and then pass into a more protracted immunosuppressive period, with the outcome largely depending on the patient’s immune system. The article focuses on understanding the role of developing disorders of innate and adaptive immunity in the pathogenesis of sepsis, their manifestations, mechanisms of immune dysfunction in septic conditions leading to impaired immune response. Bacteria that cause sepsis overcome the protective mechanisms of human immunity, which leads to the development of acute bacteremia, while the immunosuppression caused by pathogens leads to generalization of the process. Prominent bacteremia, increasing endotoxinemia due to generalization can lead to excessive activation of inflammatory, anti-inflammatory reactions and uncontrolled release of inflammatory mediators, damage to the body’s defense mechanisms, particularly, depletion of T cells, decreased expression of human leukocyte antigen (HLA)-DR on monocytes and induced uncontrolled apoptosis of neutrophils and adaptive immune cells. This leads to a worsening of sepsis course and further aggravation of immune homeostasis disorders as well as continuing enhancement of the systemic inflammatory response. Therefore, a deeper understanding of the immunological aspects of sepsis pathogenesis, which are behind the development and progression of this condition, is becoming an important part of clinical practice and is of great importance for its timely identification, improvement of treatment strategies, increase in patient favorable outcomes and lowering related mortality.

Abstract. CSF/serum ratios are the quotients of protein concentrations between the cerebrospinal fluid and blood serum. This method provides an objective assessment of proteins amount and origin in the cerebrospinal fluid. The cerebrospinal fluid protein composition consists of blood proteins passing through the blood-brain barrier and those synthesized within the central nervous system (intrathecally). Increased concentrations of proteins such as specific antibodies or autoantibodies in cerebrospinal fluid do not always mirror intrathecal synthesis or the presence of a pathological process in the intrathecal space. Elevated protein levels in the cerebrospinal fluid may be due to the higher blood protein influx through the blood-brain barrier. Quantification of CSF/Serum ratios according to German liquor specialist Hansotto Reiber allows distinguishing between blood and brain protein origin. This method is recognized as relevant for distinguishing between blood-derived and brain-derived protein fractions by the German Society for Liquor Diagnostics and Clinical Neurochemistry (Deutsche Gesellschaft für Liquordiagnostik und Klinische Neurochemie e.V.). The review is based on analyzing main literature databases (PubMed, CyberLeninka, Google Scholar, Scopus) and the latest publications on liquor diagnostics. Principles of CSF/Serum ratios, specific antibody indices calculation, and Reibergram structure are described. The classification of intrathecal inflammation and disease-related data patterns of immunoglobulin synthesis typical for diseases of the central and peripheral nervous system are presented. Thus, this literature review provides a detailed insight into the general principles of the modern approach for assessing cerebrospinal fluid protein composition and improves intrathecal humoral response comprehension. Additionally, the latest data on intrathecal immune response features in multiple sclerosis, neuromyelitis optica spectrum disorders, encephalitis associated with anti-MOG, anti-NMDAR antibodies, rheumatological diseases with CNS involvement, and neuroinfections are summarized.

Abstract. Hepatitis C is an infectious disease that causes liver inflammation and often leads to a chronic process. The genes encoding proteins involved in DNA repair systems participate in developing immune responses and inflammation, making them promising candidates for studying genetic predisposition to a wide range of common diseases, including infections. However, this group of genes is rarely studied to assess their role in genetic susceptibility to infectious diseases. In the present study, we investigated a role for polymorphisms in DNA repair system protein genes (ATM (rs189037 and rs1801516), NBN (rs709816 and rs1805800), MRE11 (rs473297), TP53BP1 (rs560191), MLH1 (rs1799977), PMS2 (rs1805321)) in the pathogenesis of chronic hepatitis C. As a result, associations were found both between some studied markers (rs1805321 in the PMS2 gene and rs1801516 in the ATM gene) and chronic hepatitis C as well as relations of various quantitative traits and the polymorphisms of these genes. For example, variability in blood biochemical parameters (levels of cholesterol, glucose, iron, prothrombin index values, and thymol test results) was shown to depend on genotypes of two markers in the NBN gene (rs709816 and rs1805800). Clinical and morphological indicators are associated with variants in the NBN (rs1805800), MRE11 (rs473297), and PMS2 (rs1805321) genes. The absolute and relative levels of neutrophils are influenced by rs1805800 (NBN), rs473297 (MRE11), and rs1799977 (MLH1), whereas lymphocyte counts are affected by both markers in the NBN gene, rs473297 (MRE11), rs1799977 (MLH1), and rs1805321 (PMS2). The lowest post-treatment IgG levels are observed in carriers of rarer genotypes in rs1805800 and rs709816 in NBN gene. Thus, our study demonstrates an impact of the studied genes on the pathogenesis of chronic hepatitis C, although the mechanism underlying such associations is not always clear. Nevertheless, our findings suggest about pleiotropic effects of DNA repair protein genes and their involvement in developing chronic hepatitis C.

Abstract. The study results showed that in the early pregnancy (up to 12 weeks) in women with a full-term pregnancy, but suffering from genital infections, changes occur in cellular immune arm. Such alterations affect both innate and adaptive immunity due to activated inflammatory reactions. At the same time, despite detected infection, pregnancy in such women may progression without serious disturbances. However, studies have shown that much more prominent changes in immune system are observed in women with former miscarriages, if they also suffer from genital infections. In women with miscarriages paralleled with genital infections, changes in the immune system are more pronounced that may be accounted for by ongoing immune response hyperreactivity. The latter is referred to an excessive reaction of the immune system to ongoing infection that results in higher inflammation. Such excessive inflammatory processes can cause a disrupted normal mechanisms of pregnancy maintenance, which in turn contributes to increased risk of pregnancy termination, as is observed in miscarriages. In addition, a more pronounced imbalance between pro-inflammatory and anti-inflammatory interleukins is observed in women with miscarriage. Pro-inflammatory interleukins (such as IL-6, IL-1β) potentiate inflammation and may increase the risk of complications during pregnancy, including miscarriage. Anti-inflammatory interleukins, on the other hand, should maintain balance in immune system and counter inflammation, but in case of women with former miscarriage, their activity is insufficient to counteract infection-related inflammatory processes. Thus, the presence of genital infections in women with former miscarriage often leads to excessive immune system activity, which contributes to increased inflammation and disrupted physiological processes that support pregnancy. In such cases, immune response is inadequate and exuberant that may contribute to pregnancy loss.

Introduction. The treatment of contaminated wounds remains a significant challenge, and the solution to this problem may lie in the realm of pathogenetic therapy. The aim of this study was to investigate serotonin-related immunoregulatory effects in a contaminated wound model in experimental animals.

Materials and methods. Wistar rats underwent surgical skin incisions in the epigastric region along the abdominal white line. Control animals received intraperitoneal saline (1st group) injections. Experimental animals were administered serotonin (days 0–5) at a dosage of 1.43 mg/kg b.w. intraperitoneally (2nd group); a serotonin pulse therapy (1.43; 1.43; 3.58; 7.15; 14.30 mg/kg) regimen was also administered (3rd group). After 5 days, the animals were euthanized, and microbiological, immunological, and histological analyses were performed. Results. Upon serotonin treatment, total microbial wound and peri-wound contamination (both hemolytic and non-hemolytic) decreased by 27% compared to control group (p > 0.05). The number of yeast-like and mold-like fungi also decreased significantly in experimental groups, by 4 times in the low dose group (1.43 mg/kg/day) and 4.6 times after pulse therapy. At the same time, an immunomodulatory effect was noted presented as increased neutrophil phagocytic activity, IL-6 levels, and activation of granulocyte lineage in the hematopoietic system. Histological analysis revealed accelerated skin regeneration in groups of treated animals.

Conclusion. Serotonin administration has an immunomodulatory effect in a model of contaminated wounds in animals, leading to reduced bacterial contamination and accelerated wound healing.

Introduction. Hepatitis B is an infectious inflammatory liver disease resulting from hepatitis B virus infection. According to the WHO estimates, 254 million people with chronic hepatitis B (CHB) were recorded worldwide in 2022. CHB is accompanied by developing liver fibrosis, which leads to impaired liver function. The progression of liver fibrosis involves multilayered cellular interactions between hepatic stellate cells, resident macrophages, and specialized immune cells. this cell interplay is regulated by humoral factors, among which cytokines play a key role. Due to this, the analysis of peripheral blood cytokines in CHB patients allows assessment of immune process activity in the liver, fibrosis progression intensity, and therapeutic effectiveness. The aim of our work was to evaluate blood plasma cytokine spectrum in CHB patients related to liver fibrosis staging.

Materials and methods. The study included 53 patients diagnosed with chronic viral hepatitis B, subdivided into three groups based on liver fibrosis stage. Blood plasma samples were collected from all study subjects. Concentration for 42 cytokines was assessed by xMAP multiplexing technology. The results underwent statistical processing using nonparametric statistical methods.

Results. Compared to apparently healthy group, CHB patients showed: significantly elevated concentrations for IL-6, IL-27, CCL11/Eotaxin, CXCL9/MIG, CXCL-10/IP-10, M-CSF; significantly decreased levels for IL-2, IL-4, IL-12(p70), IL-13, IL-17A, IFN2α, sCD40L, CCL3/MIP-1α, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CX3CL1/ Fractalkine, EGF, PDGF-AA, PDGF-AB/BB, VEGF-A. Based on different liver fibrosis stages, significant differences in cytokine levels were found between patient groups for: IL-6, IL-10, IL-12(p70), IL-27, sCD40L, CXCL9/MIG, CXCL-10/IP-10, M-CSF, PDGF-AA, PDGF-AB/BB. Correlation analysis revealed a positive relationship between liver fibrosis severity and levels for IL-6, IL-27, TNFα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and M-CSF, and a negative relationship between the severity of liver fibrosis and levels for IL-12(p70), IFN2α, sCD40L, CX3CL1/Fractalkine, EGF, PDGF-AA and PDGF-AB/BB. Thus, blood plasma cytokine spectrum in CHB patients was evaluated, identifying factors involved in CHB immunopathogenesis, including those playing a significant role for developing liver fibrosis.

Abstract. Measles, rubella and mumps are viral infections that can be prevented with highly effective vaccines. Recently, the incidence of measles and mumps has increased in many countries, involving highly immunized populations. The aim of the study was to assess measles, rubella and mumps humoral immunity in healthy people of different ages and compare these data with measles incidence in same area during the same time period. The serum samples from 713 conditionally healthy residents of different ages from Moscow and the Moscow region with an unknown vaccination history and from 700 patients with measles collected on the 4th-5th day after onset of rash were examined. Humoral immunity was determined by ELISA using the kits from Vector-Best (Russian Federation) and Euroimmun (Germany). It was found that in the group of 1–5-year-old subjects, the seropositivity rate was below 60%. Seroprevalence in groups over 6-year-old subjects against rubella fluctuates at the level of 87–94%, mumps — 72–83%. The most unstable situation was observed in humoral immunity against measles virus. In the group of 6–13-year-old subjects, seroprevalence increased to 79% followed by decline to 49.5% in group of 18–30-year-old subjects. The subsequent increase in seropositivity to 88.12% in the group over 51-year-old subjects was significantly lower than the calculated population immunity level (95%). Among measles patients in 2024, children and adolescents accounted for 54.32%. Comparison of measles incidence with the measles seronegative level in the same age groups revealed a clear pattern: the more seronegative were subjects, the higher measles incidence was in this group. In a similar study on measles incidence in 2013, all children and adolescents responded to the infection with a primary immune response, and among adult patients, a secondary immune response was detected in 12–18%. In 2024, among children and adolescents with measles, 9–12% responded with a secondary immune response, and in adult groups, the proportion of secondary response reached 44%, indicating that individuals vaccinated in childhood but who lost measles antibodies during life actively contribute to measles cases. Vaccination of seronegative grades 10–11 adolescents is necessary.

Introduction. There are conflicting data on the biological properties of hypermucoid Klebsiella pneumoniae, so in practice there are difficulties in differentiating their pathotype. The aim of the study was to compare phenotypic properties for subpopulations of hypermucoid and classical K. pneumoniae isolated from intensive care unit patients.

Materials and methods. The main group (n = 24) consisted of patients with hypermucoid K. pneumoniae, the control group (n = 24) consisted of patients infected with classical klebsiella. Isolation of K. pneumoniae from different biomaterial sources was performed by bacteriological method, identification — with “ErbaScan” microbiological analyzer using “Entero-Rapid 24” (Erba Lachema, Czech Republic). Lipase production was studied on Tributryn Agar Base (HIMEDIA, India), protease — on Micro-GELATINase (NICF, St. Petersburg), hemolysins — on 5% blood MPA (FBUN GSC PMB, Obolensk), presence of extended-spectrum β-lactamases (ESBLs) was investigated by the double-disc method, and sensitivity to phages by the SPOT test. Parametric and nonparametric statistical methods were used to process the data. The differences were considered significant at p < 0.05.

Results. The detection rate of K. pneumoniae with a hypermucoid phenotype in intensive care unit patients was 23.1%; in 66.7% of cases these bacteria were isolated from sputum. Hypermucoid K. pneumoniae had a similar frequency of virulence factors production such as lipase (70.8% and 54.2%, respectively; p = 0.927), hemolysins (45.8% and 50%, respectively; p = 0.773), proteases (12.5% and 33.3%, respectively; p = 0.086). In hypermucoid and classical klebsiella, there were no differences in the frequency of ESBLs production (75% and 62.5%, respectively; OR = 1.8; 95% CI 0.521–6.218, p = 0.351) and the frequency of bacteriophage resistance (p > 0.05). In infectious processes associated with hypermucoid klebsiella strains, the level of patient leukocytes was significantly lower than in case of classical klebsiella infections (9.7 × 10⁹ l vs 11.6 × 10⁹ l; p = 0.028). However, regardless of the pathogen phenotype, patients had similar lengths of stay in the intensive care unit (12.5–16 days; p = 0.29) and mortality rates (58.2–62.5%; p = 0.77).

Conclusion. Hypermucoid K. pneumoniae show a similar frequency of producing invasion factors, extended-spectrum beta-lactamases, and bacteriophage resistance to classical strains, which determines common approaches in the treatment of patients. The hypermucoid phenotype of bacteria is associated with lower levels of leukocytes, which must be taken into account to assess infection severity in patients.

Background. It is a well-known bacterium Proteus vulgaris that causes urinary tract infections specifically bacteriuria. This study aimed to genetically search for the role of some virulence genes in this bacterium via bacteriuria in pregnant women of the Thi-Qar Governorate of Iraq.

Materials anm methods. A mid-stream urine specimen with a total of 235 specimens was gleaned from pregnant women, which were performed in a random manner from various hospitals, when 116 cases suffered from UTI (patient group). The others (119 specimens) were collected from married women, but not pregnant women, and apparently in healthy cases (control group). MacConkey agar and blood agar were used for culturing and identification of bacteria under aerobic conditions, followed by microscopic examination, appearance description, biochemical test, API 20E analysis, and PCR analysis.

Results. Genetic analysis revealed bacteriuria in 39 (33.6%) pregnant women infected with Proteus sp., but it stooped to 3 (2.5%) in apparently healthy women (control). When phenotypically and genotypically with specific identification genes of P. vulgaris the same samples were infected with this bacterium in eight (6.8%), while it receded to 1 (0.84%) in the control. The PCR and statistical analyses demonstrated that the total existence of each study gene (ureC, mrpA, and zapA) in bacteriuria isolates of P. vulgaris was 11/9 (122.2%), 9/9 (100%) and 9/9 (100%), respectively. There was significant variation in the position of zapA on chromosomes 8/9 (88.8%) and on the plasmid that was dropped to 1/9 (11.1%).

Conclusion. The role of these bacteria is serious and significant in pathogenicity and attachment to the epithelial tissues of the urinary tract, the opportunistic nature of P. vulgaris, biofilm production, and elevated urine pH, which lead to stone production in pregnant women. PCR is the fastest and most accurate method for diagnosing P. vulgaris and its virulence genes.

Introduction. The gut microbiota represents the largest part of the entire human microbiome. The formation of a stable microbiota begins at childbirth, continuing to change during life influenced by various exogenous and hereditary factors. One of such external cues is presented by closed organized collectives, where different individuals, due to the common way of life and nutrition, undergo a restructuring of the intestinal microbial communities. In addition to microbiota quantitative and qualitative changes, inter-microbial communities may also be altered (synergism, antagonism, mutualism). The aim of the study was to analyze the synergistic and antagonistic relationships between intestinal microbial communities in individuals from closed organized collectives.

Materials and methods. The study group included 120 male subjects aged 18 to 22 years, who lived within the same closed organized collectives for 9 months. Fecal samples were selected for plating prior to living in closed organized collectives (stage 1), and 9 months afterwards (stage 2). The identified microorganisms were assigned to the permanent, supplementary, or random microbiota group. To assess the relationship between pairs of genera, the Jaccard index was calculated.

Results. The results of the study showed that the synergistic relationships between members of the permanent microbiota remain stable or increase over time, which generally corresponds to the data on the properties of the obligate microbiota. Positive synergistic relationships with additional microbiota have also been identified, e.g., between Bifidobacterium spp. and the order of Lactobacillales. The synergy of these genera can effectively support normal gastrointestinal tract functioning. However, antagonistic relationships were also noted, especially between some representatives of the additional and permanent microbiota, such as Klebsiella spp. Such data may indicate a negative effect of certain microorganisms on the intestinal microbiota in a limited collective setting.

Conclusion. Further research in this field may help explain changes in microbial communities in organized collectives and develop strategies for healthy microbiota maintenance therein.

Abstract. Peri-implantitis is one of the most common complications during dental implant installation, occuring in 10–20% cases. The main cause for such complication is the production of biofilms by bacteria colonizing the implant placement area. The triggering factor for this is dysbiosis of the commensal oral flora. Studies show that Streptococcus spp. in association with Rothia spp., Neisseria spp., Corynebacterium spp. is normally found in healthy peri-implant sulcus However, in some cases Streptococcus spp. are indicator microbiota representatives in developing peri-implantitis. Ultraviolet radiation (UV) has been actively used in dental manipulations. The aim of the study was to analyze changes in the mucosa microbiota composition in alveolar processes of the upper and lower jaws upon exposure to UV radiation. Biopsies of mucosa collected from 35 patients, applied for dental implantation, were examined. Two mucosal samples were obtained from each patient. One of either sample was treated with a “Solnyshko” UV irradiator, the second sample remained intact. As a result of the study, 60 species of microorganisms were identified divided into the following groups: the group of constant microbiota, additional microbiota, transient microbiota. The constant microbiota for both samples before and after UV treatment consisted of two Streptococcus species: S. oralis and S. mitis. After UV irradiation S. vestibularis and S. salivarius were moved into the group of additional microbiota, and N. subflava became part of constant microbiota. The widest diversity of microorganisms was found in the transient microbiota. The average number of microbial species per sample changed from 9±3 (M±SD) in samples without UV treatment to 7±3 (M±SD) in post-UV treatment samples. In the latter, microbiota composition tended to positively change. Treatment of the peri-implantation field with UV leads to lowered peri-implantitis risk, positively affects the pattern of changes in the oral microbiota, leads to reduced isolation of pathogenic microorganisms.

Abstract. The role of postmortem diagnosis is not only to establish the true cause of death, but also to provide feedback to the physician, the health care system and the patient’s relatives. Identifying the true cause of death can save sibs, future children, and sometimes even the patient’s parents. According to the 2024 classification, there are 555 different forms of inborn errors of immunity, and 17 phenocopies, but many of the patients remain undetected both in life and after death. Inborn errors of immunity (or primary immunodeficiencies) often mimic and hide under the mask of other diseases. Infections in patients with inborn errors of immunity may be atypical, persistently recurrent, and may be life-threatening, leading to death or disability of the patient. The same is true for measles, which in immunodeficient patients of any genesis may develop atypically, often with absent or delayed mucosal and cutaneous rashes, and with typical lung lesions. This article describes a clinical case of pneumonia with probable combined lesions from measles and SARS-CoV-2 viruses complicated by bacterial infection. In this case, an equilibrium translocation of long arm regions between chromosomes 7 and 18 was detected in the patient, his sibs and mother. Although this chromosomal pathology is not listed in the classification of inborn errors of immunity, the list of included diagnoses has been continuously expanding, and the presence of inborn immunodeficiency in this clinical case was confirmed morphologically. The National Association of Experts in Primary Immunodeficiencies has developed warning signs of primary immunodeficiencies that may help in the lifetime diagnosis of these diseases. Neonatal screening for the TREC and KREC markers of lymphopenia helps to identify conditions accompanied by defects in T- and B-lymphocyte maturation, and thymus ultrasound is proved to be an essential diagnostic method that helps to detect changes in thymus (one of the main organs of the immune system) size and structure during life. Morphological study, performed either at lifetime during operative thymus resection or postmortem, allows to reveal characteristic signs of immune system dysembryogenesis, including disturbance of thymus size and histological structure, decrease in the number and changes in the size of Hassall’s corpuscles. Thus, based on clinical, morphological and genetic data it reduces a chance of missing primary immunodeficiency, whereas timely diagnostics opens a window for therapeutic intervention and life-saving.