bluuebunny/crossref_metadata_2025 huggingface dataset:
Sperm DNA fragmentation and total antiradical activity of sperm in men with exaggerated anamnesis
Authors: Dolgikh O. V. , Dianova D. G. , Krivtsov A. V.
Published: April 2022

Various intracellular and extracellular stimuli can promote excessive accumulation of reactive oxygen species and lead to detrimental effects on sperm function, in particular, damage to sperm DNA, thus often resulting into infertility. The aim of the study was to assess the degree of sperm DNA fragmentation by flow cytometry and to study total antiradical activity of sperm in men with infertility and chronic prostatitis using spectrophotometric technique. A total of 75 men were examined. The comparison group consisted of 45 men with chronic prostatitis beyond exacerbation. The observation group included 30 men with chronic prostatitis in remission state. We have found that in the subjects during the period of acute inflammation, pathological fragmentation of sperm DNA was revealed, being statistically significant (p = 0.004). It was registered 1.7 times more often than in the examined men during the remission of chronic prostatitis. Increased fragmentation of the sperm DNA was noted in 50% of men from comparison group. In the patients from observation group, the degree of sperm DNA fragmentation over reference ranges was observed in 80% of the subjects. In men diagnosed with chronic prostatitis at the exacerbation stage, there is a statistically significant (p 0.05) relationship between sperm DNA fragmentation and development of acute inflammatory process. It was shown that in the subjects from observation group, the mean value of antiradical sperm activity did not show statistically significant differences (p = 0.378) compared with results found in men from the comparison group. The presented results suggest a higher degree of sperm DNA fragmentation in the examined patients with chronic prostatitis at the stage of decompensation, which may point to excessively increased production of free radicals during the acute inflammatory process. Obviously, exacerbation of chronic prostatitis contributes to imbalance in the redox homeostatic system in men, thus creating prerequisites for excess of reactive oxygen species and significant fragmentation of sperm DNA. The identified changes, i.e., an increased sperm DNA fragmentation levels and a deficiency of total antiradical activity of sperm in men with chronic urogenital diseases, may play a pathogenetic role in occurrence and further development of infertility. The degree of sperm DNA fragmentation and markers of redox processes may serve as informative activity indices of the inflammatory process.
Glycoarrays for diagnosis and therapy of the disorders of the female reproductive system
Authors: Shilova N. V. , Bovin N. V. , Nokel A. Yu. , Ziganshina M. M. , Khasbiullina N. R. , Vuskovic M. , Huflejt M. E.
Published: April 2022

The development of effective methods for prediction, diagnostics and treatment of female reproductive disorders is an urgent task. Natural antiglycan antibodies (AGAT) are of great interest in both diagnostic and therapeutic aspects, since AGATs are very diverse, and their specificities were selected in the course of natural evolution. In this work, we investigated the possibility of using glycoarray technique, as well as the signature approach to predict effectiveness of therapy in breast cancer (BC), as well as a targeted search for natural antibodies with therapeutic potential.We studied blood serum samples of apparently healthy female donors (n = 27), and patients with established diagnosis of metastatic breast cancer prior to starting therapy (n = 29). The median age of the patients was 48 years, 41% had “ER/PR+”-status, 59% – “ER/PR-“-status. The median age of healthy subjects was 50 years. The patients received combined therapy with doxorubicin and herceptin with different outcomes: 11 patients did not respond to treatment and 18 patients showed clinical response (the tumor was not revealed). For the study with AGAT, glycoarray was used, on which more than 200 different glycans were printed. The antibodies bound to the ligands were detected using biotinylated goat antibodies against human Ig (G+M+A). To search for a combination of diagnostically significant AGATs (signatures), the previously developed calculation tool “Immunoruler” was used.An opportunity of using glycoarray to predict efficiency of therapy was studied in breast cancer patients. The study included patients receiving combination therapy with doxirubicin and herceptin, with clinical response monitored at 18-24 weeks. A signature consisting of 10 AGATs with high sensitivity and specificity (90 and 91%, respectively) proved to predict efficiency of the administered therapy.The possibility of breast cancer diagnosis using AGAT has been further confirmed. The specified signature included five antibodies: the level of two AGATs was significantly higher in patients than in donors, which could be adaptive antibodies developed in response to emerging malignancy. For three other antibodies, the registered signals in patients were lower than in healthy controls, thus, probably, indicating depletion of humoral immunity during the development of breast cancer. Hence, such AGATs may have some therapeutic potential, and, by usage of glycoarray screening technology, they could be searched in purposeful manner.
Macrophage inhibiting factor in women with habitual miscarriage in pregnancy following immunocytotherapy
Authors: Vtorushina V. V. , Krechetova L. V. , Inviyaeva E. V. , Tetruashvili N. K.
Published: April 2022

The aim of our study was to evaluate the macrophage inhibitory factor (MIF) content of in peripheral blood serum, as well as MIF production by mitogen-stimulated cells from whole peripheral blood during pregnancy in women with idiopathic recurrent miscarriage who received immunocytotherapy both prior to and in the first trimester of pregnancy. The study involved 51 women 20 to 40 years old: 10 fertile healthy females beyond pregnancy, 23 women with idiopathic recurrent miscarriage (IRM), 18 women with a physiological course of pregnancy at different stages of gestation (12, in the first trimester; 12, in the second; 9, in third trimester). MIF content was assessed by multiplex analysis using flow fluorometry. Of 23 women with IRM, six lost their pregnancy in the first trimester, 14 women prolonged pregnancy to the full-term resulting into birth of a healthy child; three had premature births at 24 to 35 weeks with a live fetus. There were no intergroup differences in the serum MIF level in control women and in patients with IRM, both beyond and during pregnancy. However, the dynamics of this index during pregnancy, was similar with increase during the II and III trimesters in both groups of women (control and with IRM). During pregnancy, the dynamics of MIF production by mitogen-activated cells from peripheral blood was also similar, except for values in the II trimester: in this period, MIF production in women with IRM was significantly lower, although it was still increased 3 times compared to the 1st trimester (5-fold to controls). In women with physiological pregnancy, the serum MIF levels at 5 to 6 weeks were lower than in women in both IRM subgroups, but there was no difference in MIF content for women with miscarriage and full-term pregnancy. Similarly, there were no differences of MIF contents in the supernates of activated whole blood cells of women at the time of study within groups and between the groups at the same time of examination. It has been shown that ICT has a positive effect on the course and outcomes of pregnancy in women with pregnancy prolonged to full-term. The serum MIF content in women with full-term pregnancy is higher than in women with miscarriage, which is consistent with results of other authors about adverse developmental effects of low serum MIF levels at early pregnancy terms. The results obtained indicate that immunocytotherapy do not regularly promote pregnancy to full term in women with IPV. Therefore, further research is required to find out criteria for administering ICT in treatment of idiopathic recurrent miscarriage.
Study of relationships between maternal HLA-G gene polymorphism and intrauterine infection with risk of congenital malformations
Authors: Gordeeva L. A. , Voronina E. N. , Gareeva Yu. V. , Polenok E. G. , Mun S. A. , Glushkov A. N.
Published: April 2022

This study aims for assessing relationships between maternal HLA-G gene polymorphisms (rs41551813, rs12722477, rs41557518) and intrauterine infection with the risk of congenital malformations (CM) in infants. We studied 331 women who had offspring with CMs, and 408 women with one or more healthy children. Influence of the intrauterine infection was analyzed on the basis of laboratory tests. Diagnostics of bacterial vaginosis and vulvovaginal candidiasis by microscopic examination were conducted. Viral infections (herpes simplex virus type 2, cytomegalovirus, human papilloma virus type 16/18) as well as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Gardnerella vaginalis; Trichomonas vaginalis and Toxoplasma gondii were detected by enzyme-linked immunoassay or polymerase chain reaction (PCR) techniques. The data were obtained from the medical cards of the surveyed women. The gene polymorphisms were typed for Thr31Ser (rs41551813, HLA-G*01:03) in exon 2, Leu110Ile (rs12722477, HLA-G*01:04) and 1597 delС (rs41557518, HLA-G*01:05N) in exon 3 HLA-G using real-time PCR followed by melting analysis. The study showed that maternal age was not a significant risk factor for CMs in the fetus/newborns. Meanwhile, the maternal intrauterine infections were shown to be a significant risk factor for CMs in their infants (OR = 1.57 (1.08-2.29); p = 0.002). It was found that the 110 Ile allele (HLA-G *01:04) was a risk factor for CMs incidence in the fetus/newborns (OR = 1.57 (1.08-2.29), p = 0.01). No association was found between the maternal rs41551813 and rs41557518 HLA-G genetic polymorphisms and CMs in the infants. Hence, intrauterine infections and maternal 110 Ile allele (HLA-G *01:04) may be suggested as risk factors for birth defects in the children. Our results will be useful in understanding the molecular mechanisms of immune disorders in feto-maternal interface.
Detection frequency and duration of lupus anticoagulant circulation in COVID-19 patients
Authors: Beznoshchenko O. S. , Shpilyuk M. A. , Ivanets T. Yu. , Krechetova L. V. , Pyregov A. V. , Kodatsky D. S. , Tavluyeva E. V. , Melkumyan A. R. , Gorodnova E. A. , Dolgushina N. V.
Published: April 2022

The aim of the work was to determine frequency of lupus anticoagulant (LA) detection in patients at various degrees of COVID-19 severity as well as duration of LA circulation after the infectious disease. The study included 103 patients with COVID-19. The patients were observed during the hospital care and in ambulance, if required. The patients were admitted to the departments of infectious diseases arranged at the V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology, and F.I. Inozemtsev City Clinical Hospital. Treatment schedules and stratification of the patients by clinical severity was carried out in accordance with Interim Guidelines issued by the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of new coronavirus infection (version 9). The following groups were formed: mild (n = 27), moderate (n = 55) and severe (n = 20). The patients were tested for LA positivity in the course of disease: on the day of starting medical care (with outpatient observation), or on the day of hospitalization; repeated tests were made before discharge (inpatients), and later, 1-2 months and 7 months after recovery. Lupus anticoagulant was determined by two independent tests (dRVVT and SCT), i.e., as a screening test and a confirmation test. At initial examination, LA was found in 50 patients (49%). The effect of LA in 98% of cases was observed with dRVVT test, as an increase of normalized ratio (NR). The maximum median value of NR was 1.54 (0.97: 2.1) was revealed in patients with severe course of COVID-19 (p 0.0001) compared with other groups and correlated with severity of the infectious process (r = 0.491, p 0.0001). In mild cases of COVID-19, LA was detected less often (4 cases, 14.8%) than in moderate severity cases (27, 49.1%), and severe patients (19, 95%) (p 0.05). Re-examinations of the patients before discharge from the hospital and 1-2 months later revealed high frequency of LA (p 0.05). However, no LA-positive test was found 7 months after discharge. In patients with COVID-19, high frequency of circulating LA was registered, depending on severity of the infectious process. In addition, we have first shown that persistence of the circulating LA over post-infectious period does not exceed 7 months.
Outcomes of IVF programs with intrauterine administration of autologous mononuclear cells in women with repeated implantation failure
Authors: Vtorushina V. V. , Krechetova L. V. , Perminova S. G.
Published: April 2022

Frequency of the repeated implantation failure (RIF) in assisted reproductive technology programs remains to be high, reaching 50-75%. Intrauterine administration of autologous mononuclear cells before embryo transfer is a technique for the RIF immunocorrection being used in assisted reproductive technology programs. Direct effect of mononuclear cells upon implantation was first studied in 2006 and showed that intrauterine administration of autologous mononuclear cells prior to embryo transfer proved to significantly increase implantation frequency, as well as incidence of clinical pregnancy, and frequency of delivery in the patients with a history of RIF. The aim of this study was to evaluate the effect of intrauterine administration of autologous peripheral blood mononuclear cells prior to embryo transfer upon the results of assisted reproductive technology programs in women with a history of RIF, and to evaluate cytokine profile of the supernates from the injected cultures of peripheral blood mononuclear cells.The study included 129 women with RIF included into the assisted reproductive technology programs. The patients were divided into three groups with intrauterine administration before embryo transfer in a stimulated cycle and in a cryocycle: group 1, treated with mononuclear cells activated by human chorionic gonadotropin; group 2, with mononuclear cells without activation by human chorionic gonadotropin; group 3 who received saline solution (placebo). Clinical and anamnestic data of the women from these groups did not differ. The age of women in all three groups was also similar. The number of RIFs in their anamnesis was comparable for the 3 groups. Analysis of the embryological parameters also showed that there were no significant differences in the number of transferred embryos, including those of good quality.The levels of IL-2 (p = 0.006), IL-4 (p = 0.012), IL-5 (p = 0.012), IL-12p70 (p = 0.011), IFNγ (p = 0.012), GM-CSF (p = 0.026), and TNFα (p = 0.021) were found to be higher in the supernatants of human chorionic gonadotropin-activated mononuclear cells of women with advanced cryocycle implantation, than in supernatants of inactivated chorionic gonadotropin mononuclear cells. Frequencies of implantation and clinical pregnancy were significantly higher in the groups with intrauterine administration of autologous mononuclear cells, both in stimulated cycle and the cryocycle compared to the placebo groups.The cytokine profile of the mononuclear cell culture supernates upon intrauterine administration affects the efficiency of assisted reproductive technology programs in the women with RIF. Hence, the data obtained may allow us to develop a personalized approach to usage of various immunotherapies in assisted reproductive technology programs for the patients with a history of repeated implantation failure.
Macrophage differentiation in the tissues of myomatous nodes, depending on MRI pattern
Authors: Sotnikova N. Yu. , Malyshkina A. I. , Voronin D. N. , Nagornyi S. N. , Voskresnskaya D. L.
Published: April 2022

Macrophage differentiation is known to be regulated by specific microenvironment invaded by these cells. However, despite numerous studies on pathogenesis of uterine leiomyoma, a common benign tumor of reproductive system, the features of macrophage polarization within myoma nodes are still scarcely studied. The aim of our work was to reveal some differentiation features of macrophages which invade the tissues of myomatous nodes in the patients with different types of uterine leiomyoma (UL) dependent on MRI patterns observed. We have performed a study of 42 patients in their reproductive age with intramural UL. All the patients were subjected to MRI of pelvic area. Twelve samples of endometrium have been taken from healthy women without any signs of UL, being used as controls. UL biopsies and endometrium in its projection served as study material. Phenotype of endometrial and UL-invading macrophages was evaluated by means of multi-color flow cytometry. Expression of Activin А and RARα mRNAs was estimated in endometrial and myoma node macrophages. Likewise, collagen type 1 mRNA expression was evaluated by means of reverse-transcription real time PCR. The collagen type 1 concentration in myomatous nodes was assessed by ELISA technique. We have revealed that peripheral blood monocytes, macrophages in endometrium, and UL nodes each consist of three different subpopulations, dependent on expression levels of expression levels of CD14 and CD16 membrane receptors. For endometrium projected onto myomatous node, the ratios of “intermediate” macrophages (CD14++CD16+), and alternatively activated macrophages (CD36+) was increased, thus exerting potentially negative effects upon reproductive functions in women with uterine leiomyoma. Immediately in myomatous tissue, we have found a shift of macrophage differentiation from ‘classic’ forms towards “intermediate” and “non-classical” macrophages associated with alternative activation. However, the percentage of scavenger receptor-expressing macrophages (CD36+, CD206+) was decreased in the myoma nodes. Enhanced expression of RARα mRNA was observed in macrophages invading the myomatous nodes, whereas Activin А synthesis was higher in the macrophages invading leiomyomas with MRI pattern of simple and degenerative nodes. Imbalance between “intermediate” and “non-classical” UL-invading macrophages was associated with fibrosis, or degenerative changes of myomatous tissues, thus, probably, representing an important pathogenetic link in development of different clinical variants of uterine leiomyoma.
Variability study of immune status modified by polymorphic genetic profile in women with pregnancy loss under hydroxybenzene exposure
Authors: Kazakova O. A. , Dolgikh O. V.
Published: April 2022

The study was performed in Perm, an industrially developed Russian city where hydroxybenzene concentrations are excessive due to dust and gaseous emissions from non-ferrous metallurgic plants. Their concentrations exceed average daily and single maximally permissible amounts. Hydroxybenzene and its derivatives are hormone-like substances, thus being hazardous to female reproductive system. The goal of our study was to analyze variability of immune state influenced by polymorphic genetic profile of women with pregnancy loss under hydroxybenzene exposure. Chemical analysis of ambient air quality was performed according to MG 4.1.617-96 regulations. Biological samples were taken from 129 women with reproductive disorders at their fertile age during the five-year observation period. Hydroxybenzene contents in blood were detected with gas chromatography with inductively coupled plasma. The test group 1 included women with reproductive disorders and phenol contents in blood exceeding the reference level ( 0.016 mg/cm3 ). Test group 2 consisted of women with reproductive disorders and phenol contents in blood within standard ranges. The control group 1 consisted of conditionally healthy women with phenol contents in their blood being higher than 0.016 mg/cm3 . Control group 2 included conditionally healthy women with phenol contents in their blood corresponding to the standard values. Serotonin content in blood serum considered catecholamine regulation marker was estimated with ELISA technique; phenol-specific IgG contents were measured by means of modified competitive ELISA method. PCR technique was used for detection of ACTN3 rs1815739 gene polymorphism associated with catecholamine metabolism. We found that a half of the total study group were exposed to phenol and cresols at concentrations 1.0 MPC average daily and single maximal dose. Incidence of endometriosis among them tended to increase over the examined 5-year periodL this disorder is known to contribute to pregnancy loss. Chemical analysis of blood allowed us to reveal phenol contamination in all the women to varying degrees. Regression analysis allowed to reveal a significant dependence between phenol contents in blood and phenol-specific IgG, as well as significant correlation between blood serotonin contents and cresols concentrations (p 0.05). Kruskal–Wallis test revealed significant intergroup differences by serotonin levels. There were significant differences between the test groups 1 and 2 by serotonin contents (at p 0.0083 with Bonferroni correction). Frequencies of ACTN3 rs1815739 genotypes, using a multiplicative model, allowed us to assign T allele to the factors contributing to risk of reproductive losses induced by biological media contaminated with phenol in excess. Cross-classification analysis revealed a causal relationship between serotonin contents and ACTN3 rs1815739 genotype.
Food and inhaled allergen sensitization range in children with atopyrelated gastrointestinal manifestations
Authors: Feizer А. А. , Barilo A. A. , Smirnova S. V.
Published: April 2022

The gastrointestinal tract is a barrier to the penetration of allergens into the organism and can be one of the shock organs of the development of allergic inflammation. The diagnosis of gastrointestinal manifestations of allergies is not given due attention, since their clinical symptoms are not pathognomonic, but are identical to diseases of the gastrointestinal tract of various genesis. The aim: to study the features of the structural and functional state of the gastrointestinal tract and the spectrum of sensitization to food and inhalation allergens of children with gastrointestinal manifestations of atopy. The analysis of medical histories of children with gastrointestinal manifestations of allergies aged from 1 to 18 years (n = 28), who were treated at the Regional children's allergological center in Krasnoyarsk, was performed. All patients underwent a specific allergological examination (allergological history, determination of the concentration of total IgE, specific IgE to food and inhalation allergens). The assessment of the state of the gastrointestinal tract was carried out taking into account complaints, anamnesis, objective examination and the results of esophagogastroduodenoscopy. It is established that gastrointestinal manifestations of atopy were most often combined with dermatorespiratory manifestations of allergy in the form of allergic rhinitis, atopic bronchial asthma and atopic dermatitis. Among the lesions of the gastrointestinal tract with the highest frequency of occurrence, changes in the nature of the stool (diarrhea, constipation) and the presence of symptoms of inflammation of the gastrointestinal tract-gastroesophageal reflux, gastritis, bulbitis, duodenitis, were determined. According to the results of esophagogastroduodenoscopy, gastritis and cardia insufficiency were most often determined. According to the results of the analysis of the concentration of total IgE in the blood serum, the increased level was determined in 42,8% of cases, the average value of total IgE in the blood serum in patients with atopic genesis of allergies was 140,9 IU/ml. These data evidence that the immunopathological basis for triggering allergic inflammation of the gastrointestinal tract may be based not only on atopic mechanisms. Based on the analysis of specific IgE concentrations, the characteristics of the spectrum of sensitization to food and inhalant allergens of children with gastrointestinal manifestations of atopy were determined. The most significant allergens were: food – flour mix; pollen – mixed of trees; domestic – perennial mixed. Thus, when conducting a specific allergological examination of children with atopy, it is necessary to take into account the systemic nature of the process and pay special attention to assessing the state of the gastrointestinal tract, as one of the shock organs in the development of allergic inflammation.
Parameters of interferon system, matrix metalloproteinases and related tissue inhibitors in women with papillomavirus infection during preconceptional preparation
Authors: Nevezhkina T. A. , Knysh S. V. , Chagina E. A. , Matushkina L. S. , Umerenkova S. A.
Published: April 2022

Pregravid or preconceptional preparation comprises one of important aspects in planing pregnancy and labor that includes a set of diagnostics as well as vurative and preventive measures aimed at ensuring conception and birth of healthy children. Currently, preconceptional preparation is viewed crucial for successful conception, both provided by a woman as well as a man. Virus-associated infection is one of the main causes resulting in impaired reproductive function. Host immune response in the urinary tract is often manifested as bacterial vaginosis (BV) underlying sufficient enviroinment for developing ascending inflammatory process that accounts for its intensity and duration and lead to reproductive disorders. Our study provides the data on interferon system, matrix metalloproteinases and related tissue inhibitors in women with STDs and/or papillomavirus infection. The aim of the study was to assess level of interferons, components of matrix metalloproteinases and related tissue inhibitors in women with papillomavirus infection during preconceptional preparation. There were examined 73 patients for infection with sexually transmitted diseases (STDs) in accordance with standard protocol. All patients were divided into three groups: Group I (n = 32) – STDs with papillomavirus infection (PVI); Group II (n = 27) – STDs without papillomavirus infection and Group III – Control, consisting of 14 apparently healthy female volunteers. The average age of the patients and control subjects was 26.3±3.2 and 29.5±2.2 years, respectively. Blood serum IFN, MMP and TIMP levels were measured by using specific reagents (RD Diagnostics Inc., USA) with sandwich ELISA, according to the manufacturer’s instructions, on Multiskan immunoassay analyzer (Finland), presented as pg/ml and ng/ml. SPSS v. 20 software was used for the statistical analysis with non-parametric method. Disturbances in type 1, 2 and 3 interferons were found in women with papillomavirus infection. An increased amount of MMP-2,8,9 and related tissue inhibitors TIMP-1 and TIMP-3 in women with PVI was revealed. Long-term HPV persistence leads to developing chronic systemic inflammatory response manifested as immune-inflammatory syndrome accounting for tissue morphological changes making impossible onset of pregnancy.
Role of antisperm antibodies in the formation of infertility in varicocele and infertility
Authors: Chereshnev V. A. , Pichugova S. V. , Rybina I. V. , Beikin Ya. B.
Published: April 2022

An effect of ASA on reproductive function may be accomplished via several ways. At the present stage, despite the large number of available studies, there is no unequivocal understanding regarding prevalence of the immunological infertility in infertile males and adolescents with varicocele, who have a high risk of future infertility. Hence, it is necessary not only determining the serum and ejaculate level of antisperm antibodies (ASA) as one of prognostic infertility criteria, but also assessing their dynamic concentration depending on the degree of varicocele, after surgical correction. Objective of the study – to evaluate a role of ASA in developing infertility in infertile males of active reproductive age as well as adolescents with varicocele, to assess dynamics in serum ASA level in various age groups of adolescents, depending on the degree of varicocele, after surgical correction. For adolescents with left-sided varicocele and without varicocele, serum ASA level was measured annually at within age of subjects from 14 to 17 years, whereas ASA titer in seminal fluid was estimated at the age of 17 years. Dynamic levels of serum ACA were measured in the main vs. comparison group, between the groups based on degree of varicocele, between the groups before and after surgical correction of varicocele. 100 infertile and 30 fertile males were examined underwent a single measurement of serum and ejaculate ASA level. Anti-sperm autoimmune reactions are not the lead cause of male infertility, as none of the examined groups with reproductive pathology were highlighted by increased level of serum ASA found to be higher than the permissible normal limit. Detection of ASA in blood serum within the reference interval indicates that the hematotesticular barrier is not completely impenetrable, thereby contributing to developing immunological gamete tolerance. The degree of varicocele and surgical correction do not provoke development of autoimmune reactions against spermatozoa. Similar serum ASA levels in infertile patients and patients with varicocele without a tendency to decrease in the latter; the presence of ASA in seminal fluid requires further monitoring of such patients for timely diagnostics of developing immunological form of infertility.
Assessment of the role of WIF-1 in the genesis of ischemic heart disease
Authors: Plotnikova M. O. , Snimshchikova I. A. , Afoninа I. A. , Kulakova A. S.
Published: April 2022

Coronary heart disease poses one of the most serious threats to human health resulting in enormous physical and economic losses worldwide. WNT signaling pathways play an important role in cardiogenesis both in embryogenesis and cardiac repair after previous ischemic attacks that motivated to conduct this study. The aim of the study was to examine features of WIF-1 production in patients with coronary heart disease. There were enrolled 60 patients with a clinically verified and diagnosed coronary artery disease. WIF-1 serum concentration was measured by using enzyme-linked immunosorbent assay presenting data as absolute numbers (n, %) or medians, 1 and 3 quartiles – Me (Q0.25-Q0.75). Analyzing study data showed that WIF-1 serum concentration in patients with myocardial infarction was 2890 (1700-3337.5) pg/ml being by 7.97-fold higher than that one in healthy individuals (p 0.001), in agreement with previous studies. Moreover, in patients with angina pectoris WIF-1 serum level comprised 2170 (1493-2650) pg/ml, exceeding that one in healthy individuals by 6.14-fold (p 0.001). Thus, the data obtained regarding changes in serum WNT-inhibiting factor-1 concentration in patients with coronary heart disease expand our understanding about an impact from affected WNT-signaling pathway components in pathogenesis of inflammatory process during hypoxic injuries.
Interleukin 17A gene polymorphism in patients with rheumatoid arthritis
Authors: Stashkevich D. S. , Devald I. V. , Khromova E. B. , Evdokimov A. V. , Suslova T. A.
Published: April 2022

Interleukin 17 plays a key role in the immunopathogenesis of rheumatoid arthritis (RA) and serves as a link between activation of innate and adaptive immune cells, whereas its increased expression may represent one of the causes for uncontrolled inflammation and formation of immunopathological reactions. Among members of the interleukin 17 family, most studied is IL-17A, which is characterized by peak biological activity. IL-17A is one of the important immune mediators able to induce production of other pro-inflammatory cytokines and chemokines and promote recruitment of inflammatory cells, such as monocytes and neutrophils, into inflamed organs. IL17A gene contains a number of polymorphic sites, wherein single-nucleotide substitutions particularly at position the -197G/A may affect its expression level. Here in case-control study we retrospectively examined contribution of genetic polymorphism at the -197G/A position within the IL17A gene. Allele-specific PCR was used to iderntify the -197G/A polymorphism in IL17A gene in groups of patients with rheumatoid arthritis and healthy donors of the Russian ethnic group. Our study was made within a framework on assessing immunogenetic component for rheumatoid arthritis in ethnic Russian subjects in the Chelyabinsk Region. Prevalence of IL17A gene alleles and genotypes obtained in the work is in agreement with the Hardy– Weinberg equilibrium, and is characterized by rather high frequency of allele replacement (40%), which is typical for Caucasoid populations. Thus, it was found that interpopulation differences are characteristic of such gene polymorphism shown not to be associated with predisposition to rheumatoid arthritis in ethnic Russian subjects in the Chelyabinsk Region. Women with RA in our study were found to display certain changfes in frequencies of alleles and genotypes formed due to single-nucleotide substitution in IL17A gene at position -197G/A. However, in women such features cannot be considered as additional risk factors for developing RA. Allele -197*G, homozygous genotype -197G/G may be considered as markers of late-onset for the first RA attack in women. Analysis on distribution of SNP -197G/A alleles and genotypes within the IL17A gene showed that such polymorphism is of low value predictor likely being more associated with some RA clinical variants, but not with predisposition to RA development.
Ultrasound criteria of splenomegaly in patients with fever and infectious mononucleosis
Authors: Perepelitsa S. A. , Perminova L. A. , Stepanyan I. A. , Zakhar E. V.
Published: April 2022

Ultrasound examination of the spleen is a promising approach allowing to accurately determine its normal size in various age groups as well as in pathological conditions. Objective – to evaluate spleen size changes in patients with febrile state and infectious mononucleosis. Ultrasound morphometric examination of the spleen was carried out in patients with febrile state (group “A”, n = 22) and infectious mononucleosis (group “B” n = 24) by assessing organ echo structure, contour clarity, and its uniformity. Morphometric data allowed to measure spleen weight and various coefficients by using the method proposed by Vozgoment et al. for calculating spleen weight (Wt) with formula: Wt = 0.34 * L2h, where L – the length of the spleen, h – the thickness of the spleen (cm); spleen weight coefficient (SWC) by using the formula: 1000 m / body weight (in grams), where m – the mass of the spleen; spleen weight-to-body height ratio (KI) by using the formula: spleen weight (g) / height (cm); spleen weight-to-body surface area ratio (Ks) by using the formula: spleen weight (g) / body surface area (m2). Statistical analysis was performed by using Statistica 10.0 software package. Febrile state in most cases is not accompanied by changes in spleen size. However, decreased spleen size was found in one (4.5%) patient aged 58 years, whereas splenomegaly – in 2 (9%) cases (SWC range 5.5- 5.9) in young patients aged 18 and 25 years. The course of infectious mononucleosis in 25% cases was not accompanied by change in spleen size. In other cases, both decreased (20.8%) and increased (54.2%) spleen size were observed. In particular, decreased spleen size was detected in patients with average age of 43.6±14.5 years, whereas increased spleen size (SWC range 4-8.9) was typical for young people aged 25±8 years. Febrile state in most cases is not paralleled altered spleen size. Infectious mononucleosis was associated with the three types of altered spleen size: no change, decreased spleen size characteristic to older patients, or increased spleen size observed in young subjects. Ultrasound examination of the spleen with measuring its morphometric parameters represent objective criteria allowing to fully assess the state of this immune organ and reveal degree of its involvement in the pathological process at the preclinical level.
Features of peripheral blood B cell phenotype in patients with pressure ulcers
Authors: Borisov S. A. , Savchenko A. A. , Kasparov E. V. , Fokin V. A. , Matsenko M. V. , Kudryavtsev I. V. , Borisov A. G.
Published: April 2022

Pressure ulcers represent most common surgical pathology in the pattern of nosocomial complications. However, no unified mechanism leading to development of pressure ulcers has been proposed yet despite the lead role played by compression and immobilization. In this regard, examining immune system as the main component maintaining integrity of anatomical barriers in the skin and mucous membranes seems highly promising for creating new methods to prevent and treat pressure ulcers. Our study was aimed at investigating phenotypic profile of peripheral blood B cells in patients with pressure ulcers. There were enrolled 67 patients complicated with pressure ulcers at the Department of Surgery. Examination of pressure ulcers included determining anatomical localization, investigating depth (degree) and size of the lesion (by measuring wound area), skin color and assessing nature of pressure ulcer edges and edema, wound bottom, presence of cavity with tendons and/or bone formations may be recognized therein, characteristics of exudate (smell, color), pain sensation. In control group there were included 81 apparently healthy subjects. All groups contained age- and sex-matched subjects. Phenotyping of peripheral blood B cells was performed by using flow cytometry with panel of monoclonal antibodies. It was found that count of B cells in patients did not change in parallel with increased total lymphocyte count, but was associated with their functional activity (increased percentage of CD23- and CD38-positive B cells). Moreover, percentage of B1 and naive B2 cells declined in patients with pressure ulcers that seemed to be associated with the premorbid background of the main disease, lack of adequate wound healing process coupled to tissue necrosis and damage to skin capillaries. The more severe the clinical course of pressure ulcers (regarding area and stage of development), the smaller percentage of B2 cells (both naive and memory B cell subsets) was detected in the patient peripheral blood. At the same time, changes in the B cell phenotypic profile from patients are associated with the area of lesion, but not with the stage of developing pressure ulcers evidencing that B cells affect healing of pressure ulcers. The features of B cell phenotype promote unfavorable disease outcome evidenced by the lack of quantitative differences in B cell lineage composition or level of surface expression for activation markers.
Sensitivity of archival and clinical enterobacteria strains to synthetic GM-CSF active center ZP2 peptide
Authors: Zurochka A. V. , Dobrynina M. A. , Zurochka A. V. , Gritsenko V. A.
Published: April 2022

Objective: to study sensitivity of various enterobacterial species to the bactericidal action of the ZP2 synthetic GM-CSF active center peptide after long-term storage. In vitro experiments were carried out with archival archival test strains Escherichia coli K12 (GISK 240367) and E. coli (ATCC 25922), as well as 104 clinical isolates of E. coli (n = 22) and Klebsiella pneumoniae (n = 82) obtained from patients with surgical pathology. The bactericidal effect of the ZP2 peptide (final concentration 10 μg/ml) on microorganisms was assessed by measuring optical density (OD) difference between experimental and control broth cultures after 20 min exposure of bacterial suspensions (5 × 108 CFU/ml) with the ZP2 peptide (in control – with distilled water), added with meat-peptone broth and incubated at 37 °C for 4 hours. The ZP2 peptide effect was presented as Bactericidal Activity Index (BAI, %). It was experimentally found that the archival E. coli test strains as well as most of examined clinical strains of E. coli and K. pneumoniae (95.5 and 97.6%, respectively) showed sensitivity to the bactericidal effect of the synthetic ZP2 peptide (at a final concentration of 10 μg/ml ) with BAI averaging 77.6±3.5 and 82.8±1.6% and its relatively wide variation range 45.8 ... 98.9 and 42.1 ... 99.8%, respectively. The 5-year storage of synthetic ZP2 peptide at 8 °C exerted bactericidal effect on antibiotic-resistant enterobacterial strains. The data obtained can be used to develop ZP2 peptide-based drugs aimed at combating pyo-inflammatory processes caused by antibiotic-resistant E. coli and K. pneumoniae strains.
Features of altered immune status in acute brain concussion
Authors: Norka A. O. , Vorobyev S. V. , Kuznetsova R. N. , Serebriakova M. K. , Kudryavtsev I. V. , Kovalenko S. N.
Published: April 2022

Traumatic brain injury (TBI) is one of the most common type of injuries, so that its mild form prevails in overall injury pattern. Currently, it is known that brain injury triggers immune system response, but its role in translating into clinical manifestations, potential complications and sequelae remains poorly understood. It necessitates assessment of cellular immunity in patients with acute TBI of varying severity followed by investigating relationship between identified changes. It is now believed that immune system plays a lead role in brain functioning. It may be accounted for by interplay between peripheral immune cells and the brain, which may become augmented during developing immune response. Here we quantitatively assessed composition of major peripheral blood helper T cell subsets in TBI patients by flow cytometry measuring percentage of central (CM, CD45RA-CD62L+) and effector (EM, CD45RA-CD62L-) memory Th cells. It was found that percentage of Th17 (CXCR5-CXCR3-CCR6+CCR4-), DP Th17 (CXCR5-CXCR3+CCR6+CCR4+) within CD3+CD4+T cell population were significantly increased (p 0.05) compared to control group. Moreover, percentage of Th1/Th17 subset (CXCR5-CXCR3+CCR6+CCR4-) was significantly increased (p 0.05) within EM and CM T cell subsets compared to control group. In addition, percentage of Th1 (CXCR5-CXCR3+CCR6-CCR4) was also significantly elevated in CD3+CD4+, EM and CM T cells compared to apparently healthy subjects. Hence, the data obtained allow to consider immune reactions among crucial arms in TBI pathogenesis related to concussion and its consequences. Thus, brain concussion affects cellular immune response triggering distortion in CD3+CD4+T cell composition as well as percentage of helper central and effector memory T cells. Hence, the changes revealed in patients with acute brain concussion may predetermine disease course and developing long-term complications, which requires advancing therapeutic and rehabilitation protocols in such patients.
Translation into Russian of the Classification of inborn errors of immunity in humans updated by experts from a Committee on Congenital Immunity Errors of International Union of Immunological Societies (Russian version 2019)
Authors: Bolkov M. A. , Tuzankina I. A. , Shinwari Kh. , Cheremokhin D. A.
Published: April 2022

We present to Russian-speaking audience a translation and commentary on the classification of inborn errors of immunity presented at the end of 2019 by the Committee on Congenital Immunity Errors at the International Union of Immunological Societies (IUIS). Inborn errors of immunity, or, as they were called earlier, primary immunodeficiencies, is a rapidly expanding class of diseases that includes the most diverse congenital pathologies which can manifest at any age by heterogenous symptomes. Clinical masks characterize these diseases, hence the time from the onset of clinical disorder to the final diagnosis may take many years. A doctor of any specialty encounters these patients, and the molecular mechanisms of pathology concern different organs and systems of the patients. The classification consists of ten tables covering more than 400 syndromes and their corresponding genes, or associated chromosomal abnormalities. This is a tool, which allows navigating a wide variety of different primary immunodeficiencies, autoimmune and autoinflammatory syndromes, complement defects, and bone marrow failure syndromes. We hope that, due to translation, current knowledge about these various diseases will become more close and available to the Russian-speaking audience.
Immune reactions to clinical carcinogens and steroid hormones in breast pre-cancer and cancer patients
Authors: Glushkov A. N. , Polenok E. G. , Gordeeva L. A. , Mun S. A. , Kostyanko M. V. , Kolpinckiy G. I. , Vafin I. A. , Antonov A. V. , Verzhbitskaja N. E.
Published: April 2022

Detection of postmenopausal women at high risk for breast pre-cancer and cancer is a key condition to prevent these diseases. Aim of our research was to study possible usage of immunoassay for antibodies specific to benzo[a]pyrene, estradiol, and progesterone (IgA-Bp, IgA-Es, IgA-Pg) in determination of personal risks for fibrocystic disease and breast cancer at the early stage, with respect to hormone receptor status in tumor tissues. Blood serum IgA-Bp, IgA-Es, IgA-Pg were studied by ELISA in postmenopausal women: healthy controls (n = 401), patients with fibrocystic breast disease (n = 50), and breast cancer (stage I, n = 575, stages II-IV, n = 861). High individual IgA-Bp/IgA-Pg ratios of 1.5 were found in 19.7% of healthy women, and in 50.0% of fibrocystic breast disease patients (p 0.0001; OR = 4.1). IgA-Es/IgA-Pg ratios of 1.0 were revealed in 48.4% healthy women and in 68.0% fibrocystic breast disease patients (p 0.01; OR = 2.3). IgA-Bp/IgAPg values 1.0 were found in 41.9% of healthy women, and, at higher rates, in the patients with breast cancer stage I: 68.3% ER- tumors (p 0.0001; OR = 3.0) and 75.9% ER+ tumors (p 0.0001; OR = 4.4). IgA-Es/ IgA-Pg ratios 1.0 were revealed in 48.4% of healthy women, and in patients with breast cancer stage I: 65.3% ER- tumors (p 0.003; OR = 2.0), and 76.8% ER+ tumors (p 0.0001; OR = 3.5). Some associations of studied antibodies with cancer progression were revealed. Frequency of individual cases with IgA-Bp/IgA-Pg 1.0 in patients with ER- tumors increased from 12.0% at stage I to 19.9% at stage II. Frequency of cases with IgA-Bp/IgA-Pg 1.0 in the patients with ER+ tumors decreased from 62.0% at stage I to 57.3% at stage II (p = 0.002). Frequency of cases with IgA-Es/IgA-Pg 1.0 in the patients with ER- tumors increased from 11.5% at stage I to 21.4% at stage II. Frequency of cases with IgA-Es/IgA-Pg 1.0 in patients with ER+ tumors decreased from 63.3% at stage I to 56.1% at stage II (p 0.001). The cases with individual excessive IgA-Bp and IgA-Es levels are associated with fibrocystic breast disease and ER+ breast cancer at the onset of the disease. Breast cancer progression was associated with the relative decrease of ER in tumor tissues, along with higher individual levels of IgA-Bp and IgА-Es and lower IgA-Pg levels. ELISA testing of IgА-Bp, IgА-Es, IgA-Pg could be recommended for detection of individual risk for fibrocystic breast disease and stage I of breast cancer, as well as for more efficient prevention and therapy by selective modulators of estrogen receptor (raloxifene, arzoxifene and lasofoxifine) and aromatase inhibitors (exemestane, anastrozole).