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Introduction. Serological diagnosis of inflammatory bowel diseases (IBD) is an additional tool not only for differential diagnosis, but also for individual prediction of the clinical course and long-term outcomes of Crohn’s disease (CD) and ulcerative colitis (UC).The objective was to assess the occurrence and capabilities of determining antibodies to Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) in predicting the clinical outcomes of IBD.Methods and materials. The study included 71 patients with CD, 26 with UC, and 21 with and 21 with IBD unclassified (IBDU). The comparison group consisted of 35 patients with other gastrointestinal diseases (irritable bowel syndrome with diarrhea (IBS-D), celiac disease, autoimmune gastritis (AIG)); the control group consisted of 24 apparently healthy individuals. The level of antibodies to ASCA IgA and IgG was measured by the ELISA method (ORGENTEC Diagnostika GmbH, Germany), ANCA IgG was determined by the IIF method of the Granulocyte Mosaic test system (EUROIMMUN AG, Germany).Results. The occurrence of ASCA IgA and IgG in patients with CD was 25 % and 38 %, which is significantly higher compared to patients with UC (0 % and 3.8 %), IBDU (5 % and 5 %), AIG (0 % and 5.3 %) respectively (p

In the last decade, pathogenetic methods for the treatment of spinal muscular atrophy 5q have been developed. These include increased expression of the SMN2 gene, correction of SMN2 splicing, or reexpression of the SMN1 gene. Despite the comprehension of the genetic causes of the disease and the existence of therapies, it is still not completely known which molecular mechanisms in SMN protein deficiency lead to the degeneration of motor neurons. Understanding the molecular pathways involved in the loss of motor neurons may help develop new therapeutic strategies. The article presents genetic and biochemical data that reveal the molecular mechanisms of neurodegeneration in spinal muscular atrophy 5q.

Introduction. Non-alcoholic fatty liver disease in most cases is closely associated with diseases such as obesity and type 2 diabetes mellitus, however, this dependence is not observed in a number of patients. In this case, hereditary factors, such as the p.I148M polymorphism of the PNPLA3 gene, play the greatest role in the prognosis of the course of the disease.The objective of the study was to evaluate the effect of the p.I148M polymorphism of the PNPLA3 gene on the course of NAFLD in subgroups of patients with and without concomitant metabolic pathology.Methods and materials. The study group included 212 patients with NAFLD who underwent p.I148M genotyping of the PNPLA3 gene. The severity of the disease was assessed in the general group (group P) and in subgroups of patients with the absence and presence of obesity (subgroups O– and O+, respectively) and type 2 diabetes mellitus (subgroups D– and D+). The severity of the disease was assessed by the severity of cytolytic syndrome (ALT level), hepatic steatosis and fibrosis (the value of CAP and liver stiffness according to transient elastometry) within clinical subgroups between carriers of different PNPLA3 genotypes.Results. Higher ALT levels were found in homozygous carriers of p.I148M compared with the reference genotype (CC/GG) in the subgroups P, D–, D+ and O– (p=0.012; p=0.012; p=0.028 and 0.042, respectively), as well as when comparing the general group of carriers with reference genotype (CC/CG+GG) in subgroups P and D– (p=0.036 and p=0.015). More severe steatosis was found in homozygous carriers compared to the reference genotype (CC/GG) in group P (p=0.017) and subgroup O– (p=0.019). Higher values of liver stiffness were noted in the modified PNPLA3 genotype when comparing the reference (CC/CG) genotype with heterozygotes in group P (p=0.027) and subgroup D– (p=0.006) and when comparing the reference genotype with the general carrier group (CC/CG+GG) in subgroup D– (p=0.009).Conclusions. The carriage of p.I148M of the PNPLA3 gene in patients without metabolic disorders (obesity, type 2 diabetes mellitus) is associated with the formation of cytolytic syndrome, steatosis and liver fibrosis.

Relevance. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and sustained production of autoantibodies.The aim of the study – to compare composition of peripheral blood cytotoxic CD8+ T lymphocytes (Tc) subsets and assess the clinical significance of them in systemic lupus erythematosus. Materials and methods. A total of 35 SLE patients and 49 healthy volunteers were included in the study. Phenotyping of peripheral blood T cell subpopulations was carried out by means of flow cytometry. T lymphocytes were determined using CD3+, CD4+, CD8+ antibodies. Tc were identified by using CD45RA and CD62L antibodies. Also the expression of chemokine receptors (CCR4, CCR6, CXCR3 and CXCR5) on Tc cells was assessed and the main Tc subpopulations were determined: Type 1 (Tc1), type 2 (Tc2), type 17 (Tc17), type 17/1 (Tc17.1), type 17/22 (Tc17.22) cytotoxic cells and T follicular cytotoxic cells (Tfc).Results. The absolute and relative number of Tc was significantly higher in the group of patients with SLE compared with the control group. Additionally, there was a significant decrease in the relative number of Tc1, Tc 17.1 and Tfc1 and a significant increase in the relative number of Tc2, Tfc 17 and Tfc17.1 within the SLE group when compared to the control group. There were significant positive correlationfor Tc1 and levels of C3 and C4 complement components (r=0.404, p

Traumatic brain injury (TBI) results in a significant inflammatory burden that increase the production of inflammatory mediators and biomarkers. The immune system plays a key role in the pathogenesis of traumatic brain injury. Neuroinflammatory mediators released from resident glia (activated microglia and astrocytes) inside the brain recruit immune cells where cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. Interleukin-6 (IL-6) is a proinflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. The purpose of the current study was to assessment of cerebrospinal fluid (CSF) interleukin-6 (IL-6) and MBP levels in patients with TBI. Samples of cerebrospinal fluid of 85 patients with TBI were examined. Concentrations IL-6 were measured via xMAP multiplexing technology. The control was the course of CSF in patients with concussion. An increased content was found in all patients with traumatic brain injury: 19.59 pg/mL in the group with mild traumatic brain injury; 103.6 pg/mL in the group with moderate traumatic brain injury; and 2225 pg/mL in the group with severe traumatic brain injury load versus 2.58 pg/mL in the control group. A direct correlation was found with the presence of basic myelin proteins in the cerebrospinal fluid, which indicates the degree of damage and neurodegeneration processes. Identification of the features of IL-6 content in patients with brain injury may indicate its important role in the course of disease. It also requires additional more detailed study, including comparison with IL-6 content in peripheral blood.

Introduction. Perioperative FLOT chemotherapy has improved prognosis in patients with locally advanced resectable gastric cancer (GC). However, in 80 % of cases, the tumor is resistant to the therapy, resulting in unnecessary toxicity and delayed surgical treatment.Aim. Evaluation of clinico-morphological patterns of microsatellite instability, HER2 gene amplification, changes in gene copy number and their relationship with the response to perioperative FLOT chemotherapy in patients with locally advanced resectable GC.Materials and methods. The retrospective study included 185 patients. All tumor samples were assessed for HER2 and microsatellite instability status. Among all cases there were 45 patients with locally advanced T2–4N1–2 M0 GC, who underwent a total or subtotal gastrectomy with D2 lymphadenectomy and perioperative chemotherapy with FLOT. Microsatellite instability detection was performed using fragment analysis, HER2 gene amplification testing – fluorescent in situ hybridization. Also 19 patients were tested for copy number changes of the FGFR1, FGFR2, KRAS, MET, EGFR, CCND1, MYC genes using Multiplex ligation-dependent probe amplification. The endpoints were progression-free survival and objective response rate.Results. Microsatellite instability was detected in 4.8 % (9/185) of GC cases. Microsatellite instability was associated with advanced age (p = 0.005), low grade of differentiation (p = 0.011), presence of tumor-infiltrating lymphocytes (p = 0.0004), and high preoperative CA 72–4 levels (p = 0.025). Prevalence of HER2 amplification was 7.5 % (14/185). It was associated with low grade of differentiation (p = 0.048) and metastasis in regional lymph nodes (p = 0.037). PFS in patients with HER2-positive (HER2 – human epidermal growth factor receptor 2) GC treated with perioperative FLOT chemotherapy (4/45) was significantly lower than in patients with HER2-negative GC: the median was 156 and 317 days, respectively (hazard ratio 0.49; 95 % confidence interval 0.16–1.47; p = 0.0006). There was no correlation between the presence of the alteration and ORR (p = 1.0). Progression-free survival in GC patients with KRAS amplification (3/19) was significantly lower comparing with patients without it: the median was 98 and 327 days, respectively (hazard ratio 0.29; 95 % confidence interval 0.07–1.19; p 0.05).Conclusion. The presence of HER2 and KRAS amplification have been shown as promising predictive markers of the treatment failure in patients treated with perioperative FLOT chemotherapy for locally advanced resectable GC.

The objective: to evaluate the feasibility of using dexamethasone and lidocaine to potentiate the effect of anesthesia in patients with chronic polypous rhinosinusitis during functional endoscopic sinus surgery (FESS) interventions.Subjects and Methods. Clinical data, blood serum samples were collected prospectively from 52 patients who underwent FESS intervention. The patients were divided into 3 groups: Control Group ‒ C (n = 26), anti-inflammatory drugs were not administered; Dexamethasone Group ‒ D (n = 13), dexamethasone was administered (0.10‒0.15 mg/kg); and Lidocaine Group ‒ L (n = 13), a 1% solution of lidocaine was administered intravenously. The following parameters were studied: IL-6, IL-10, IL-18, alpha1-antitrypsin, and ferritin.Results. An increase of IL-6, IL-6/IL-10 was observed in Group C. An increase of IL-10 and a decrease of IL-6, IL-6/IL-10 were noted in Group D. In Group L, IL-6, IL-6/IL-10 did not change significantly. The intensity of bleeding was lower in Groups L (p < 0.001) and D (p < 0.05) versus Group C. Relative changes in the concentration of biomarkers within the normal range were detected in all groups.Conclusions. Changes in the cytokine profile are insignificant in patients with chronic polyposis rhinosinusitis during FESS performed under combined anesthesia.No convincing data on the need for intraoperative use of dexamethasone or intravenous lidocaine have been received.

Background. Proximal spinal muscular atrophy 5q (5q‑SMA) is one of the most common neuromuscular diseases, which is caused by mutations of the SMN1 gene. Despite the fact that most studies consider SMN1 “deletion” as the most common cause of 5q‑SMA, gene loss is in fact associated with both classical deletions and conversions of SMN1 and SMN2, as well as with formation of chimeric structures. Up to now, far too little attention has been paid to the prevalence of types of SMN1 loss. However, different types of mutations can have different influence on the clinical findings and the effectiveness of therapy. A deeper study of the structure of these genes will allow us to determine the predictors of response to treatment and bring us closer to understanding the reasons for the instability of the SMN region.Aim. To study genetic changes in the SMN1 gene, as well as the number of copies of the SMN1 and SMN2 genes in 5q‑SMA.Materials and methods. The study involved 703 patients, for whom the analysis of the number of copies of SMN1 and SMN2 was performed in the center of molecular medicine of I.P. Pavlov First Saint Petersburg State Medical University for 2018–2021. Gene copy number analysis was performed by multiplex ligation‑dependent probe amplification (MLPA) using the SALSA MLPA P021 SMA kit (MRC Holland).Results. Among 703 participants, a homozygous SMN1 deletion was found in 167 (24 %), 76 (11 %) were carriers of the deletion and no aberrations were found in the remaining 460 (65 %). Among patients with a homozygous deletion, 41 (24 %) cases of a true deletion were identified. Also, 11 (7 %) cases of partial deletion with a homozygous loss of the 7th exon and heterozygous of the 8th exon of SMN1 were identified. The most common type of aberration was the conversion of SMN1 to SMN2 – 94 (56 %) cases, which is characterized by a homozygous loss of SMN1 and a reciprocal increase in SMN2 copies. In addition, 21 (13 %) cases of the formation of hybrid genes were found.Conclusion. Types of genetic aberrations in 5q‑SMA have not been studied enough yet. A search of the literature revealed very few studies which results are comparable with ours. However, further research of genetic changes in SMN1 and SMN2 might bring more clarity on the causes and mechanisms of this disease, and get us closer to finding the most effective method of treatment.

Introduction. Fine needle aspiration biopsy followed by cytological examination is the gold standard in the diagnosis of thyroid nodules. However, up to one third of cases represent an indeterminate result (Bethesda Thyroid Classification, 2017) III—V). Among such cases, category IV is the most common and most difficult to interpret (Bethesda, 2017). The study objective is to determination of the diagnostic and prognostic significance of the molecular genetic study of the fine needle aspiration biopsy material in patients with thyroid nodules with the cytological category Bethesda, IV.Materials and methods. The study included surgical thyroid samples obtained from patients whose cytological examination revealed pathology of cytological category IV according to the Bethesda classification (2017). group 1 included surgical samples from 143 patients with thyroid lesions, and group 2 - cytological material from 45 patients. Determination of the BRAF V600E mutation, mutations in the RAS genes (KRAS, HRAS, NRAS) was carried out using allele-specific polymerase chain reaction, and the RET / PTC1, RET / PTC3 and PAX8 / PPARG translocations were determined using reverse transcription polymerase chain reaction. Sanger sequencing was used to detect mutations in the promoter region of the TERT gene.Results. In group 1, an overall prevalence of the studied mutations in thyroid cancer was 35.1 %: 8.8 % of cases were mutation BRAF V600E, 24.6 % - mutations in the RAS genes, 1.8 % - mutation C228T in the TERT gene. The C228T mutation in the TERT gene was found in 1 case of widely invasive Hurtle cell carcinoma. The prevalence of mutations in benign formations was 4.7 %. mutations in RAS genes were also found in them in group 1, mutation BRAF V600E was associated with the presence of extrathyroid invasion (p = 0.024), vascular invasion (p = 0.018), and lymph node metastases (p = 0.018). In group 2, using the genetic panel sensitivity and specificity were equal: 36.4 and 93.9 %, respectively. positive and negative predictive values were 66.7 and 81.6 %, respectively. No RET / PTC and PAX8 / PPARG translocations were found in groups 1 and 2.Conclusion. The investigated molecular genetic panel, having a high specificity for carcinomas, will make it possible to supplement the cytological diagnostics of material in the category Bethesda, IV. BRAF V600E was associated with an aggressive morphological pattern.

Secondary hemophagocytic syndrome (sHLH) is a hyperinflammatory reaction which manifests with fever, cytopenia and organ damage. possible causes of sHLH include leishmaniasis. The article describes a clinical case of sHLH in patient with visceral leishmaniasis. A female 30 years old developed hectic daily fever up to 40 °C, pancytopenia, cytolytic syndrome, hyperferritin- and hypertriglyceridemia, immunoglobulin G to capsid antigens of the Epstein-Barr virus, enlarged liver and spleen a one and a half month after returning from Spain. based on the HLH-2004 and H-Score criteria, a sHLH was diagnosed, presumably associated with the Epstein-Barr virus. Immunosuppressive treatment with dexamethasone, cyclosporin-A and etoposide was started under the HLH-2004 program. Apyrexia, reduction of splenomegaly and resolution of cytolysis were achieved. The fever resumed 20 days after the start of chemotherapy, the spleen enlarged again, and therefore a diagnostic splenectomy was performed. Morphological analysis of the removed spleen revealed leishmania. After amphotericin-B therapy, the patient recovered. Chemotherapy of sHLH led to a temporary improvement for a period sufficient to verify the diagnosis and conducting of successful treatment.

Adult-onset Still’s disease (AOSD) is a rare complex autoinflammatory disease of unknown etiology. The main problem, practitioners have been facing with when researching AOSD, is the lack of developed approaches to assessing the activity of the disease. Traditionally used standard markers of inflammation do not always reflect the real activity of AOSD, especially when a patient is already receiving anti-inflammatory therapy. The article presents original data on the study of biomarkers: interleukin-1 beta (IL-1b), interleukin-6 (IL-6), interleukin-18 (IL-18), ferritin, glycosylated ferritin, calprotectin, procalcitonin compared with C-reactive protein, leukocyte and neutrophil counts in patients with moderate and high activity of AOSD. The relationship between inflammatory biomarkers and the Pouchot systemic score was evaluated to identify promising laboratory indicators of disease activity.

Introduction. The emergence of new markers that determine the choice of therapy for metastatic colorectal cancer (CRC) has led to an increase in overall survival. The optimal treatment tactics now take into account both clinical and molecular-genetic characteristics of the tumor.Aim. Investigation of the features of the KRAS, NRAS and BRAF mutations and amplification of the HER2 gene depending on microsatellite instability (MSI) in CRC.Materials and methods. The study included 400 patients with CRC. MSI, BRAF V600E mutation, mutations in the KRAS and NRAS genes was identified to them. MSI was determined by fragment analysis, and mutations in the KRAS, NRAS, BRAF genes by realtime PCR. HER2 amplification was determined in 100 patients with a negative RAS/BRAF. NTRK translocations were determined in all patients with MSI. Data on preoperative levels of CEA and CA19-9 were obtained from 185 patients.Results and discussion. The prevalence of MSI was 6.8%. The prevalence of KRAS, NRAS, BRAF mutations in CRC with MSI was 66.7%, and in CRC with MSS - 52.3%. In patients with MSI, the level of CEA was lower than in MSS (p = 0.0061). The overall prevalence of KRAS and NRAS mutations was 45% and 2.5%. The overall prevalence of the BRAF V600E mutation was 5.8% and was more common in MSI-positive tumors (p < 0.0001). Regardless of MSI, BRAF-positive tumors were characterized by right-sided localization (p < 0.0001), category T3-4 (p = 0.013), lymph node involvement (p = 0.004), carcinomatosis (p = 0.046), high levels of CA19-9 (p = 0.014). HER2 amplification was found in 7% of wild-type RAS/BRAF cases and was associated with rectal cancer (p = 0.044), category T3-4 (p = 0.041), and distant metastases (p = 0.038). HER2 amplifications and NTRK translocations were not detected in cases with MSI.Conclusion. MSI-positive CRC had a higher prevalence of mutations in major genes. CRC with the BRAF V600E mutation and HER2 amplification had aggressive clinical and morphological parameters.

Itroduction. Immune checkpoint inhibitors have become the standard of care for patients with advanced non-small cell lung cancer. However, despite the determination of programmed death-ligand 1 expression in clinical practice, which determines the effectiveness of therapy, up to 80 % of patients with non-small cell lung cancer do not respond to treatment.The study objective – investigation of the prognostic role of clinical and immunological markers during immune checkpoint inhibitor monotherapy in ≥2 lines in patients with advanced non-small cell lung cancer.Materials and methods. The study included 45 patients with advanced non-small cell lung cancer receiving programmed cell death 1 / programmed death-ligand 1 inhibitors in monotherapy in 2 and subsequent lines (Group 1), as well as 30 patients with advanced non-small cell lung cancer receiving first-line chemotherapy (Group 2). All patients from 2 groups did not have autoimmune diseases before starting treatment. The determination of autoantibodies, β-2-microglobulin, neopterin, interleukin 6, interleukin 18 and the allelic variant of HLA-DRB1 in patients in the Group 1 was carried out 2 months after the start of therapy, and in the Group 2 – before the start of the next chemotherapy cycle.Results. In Group 1, the presence of EGFR / ALK mutations is an independent predictor of shorter progression-free survival (p = 0.018). Also, in the univariate analysis, neutrophil-lymphocyte ratio

Abstract Background Patients with celiac disease present with not only gastrointestinal symptoms but also extraintestinal manifestations such as anemia, osteopathy, dermatitis herpetiformis, and celiac neuropathy. Despite a fairly wide range of celiac neuropathies, we report a case of the acrodystrophic variant of celiac polyneuropathy, which has not been previously described. Case presentation A 41-year-old Ukrainian male suffered from symmetric, sensorimotor axonal polyneuropathy and encephalopathy associated with celiac disease, which is characterized by severe trophic disorders in the lower extremities (trophic ulcers, hyperkeratosis, and anhidrosis). Acrodystrophic changes in the lower extremities were due to both neurogenic and direct immunoinflammatory damaging effects. Clinical–electrophysiological dissociation was also noted, which was represented by a gross axonal lesion with the preservation of muscle strength. The absence of enteropathic manifestations was accompanied by the pronounced histological changes in the duodenal mucosa by IIIb stage of Marsh. A gluten-free diet in combination with membrane plasma exchange and intravenous pulse methylprednisolone was prescribed to reduce the severity of sensory disorders and regression of encephalopathy within 7 months. Conclusion Celiac disease may be a potential cause of neuropathy and encephalopathy in adult patients. Further immunosuppressive treatment protocols for both intestinal and extraintestinal manifestations of celiac disease are required.

Anti‑NMDA encephalitis is a rare autoimmune disease of the central nervous system caused by the synthesis of autoantibodies to the NR1/NR2 subunits of the NMDA receptor, characterized by the development of acute mental, cognitive, motor, autonomic disorders, epileptic syndrome and central hypoventilation.The article presents a three‑year observation of patient 34 years old with anti‑NMDA ncephalitis associated with late‑ stage ovarian teratoma, accompanied by an increase titer of antibodies to NMDA receptors in serum to 1:640.Based on a detailed analysis of clinical, neurological, neuropsychological (MMSE, MoСA, FAB, 10 words test A.R. Luria) and laboratory‑instrumental characteristics of the disease (titer anti‑NMDA, level of IgG, IgM, IgA, lymphocyte subpopulations, EEG, MRI of the brain, pelvis) suggested a combination scheme of first and second line therapy. The sequential use of two cycles of medium‑volume membrane plasmapheresis (25–30 % of the circulating plasma volume, No. 5 + 5) was carried out in combination with pulse therapy with methylprednisolone 1.0 (No. 4 + 3) and cyclophasphamide 1.0 (No. 2 + 1) on background of persistent ovarian teratoma. Symptom regression was achieved by the end of the first cycle, and full recovery to the initial level of cognitive functions occurred after the second cycle, while maintaining the anti‑NMDA antibody titer to 1:160. After removal of ovarian teratoma, the level of anti‑NMDA decreased in a month to 1:40, and after 7 months it reached normal values (

Proliferation and hyperactivation of B-lymphocytes in the salivary glands is a feature of primary Sjцgren's syndrome (pSS). Detection in saliva of proteins synthesized by B-lymphocytes may be important in the diagnosis of this disease.Objective: to evaluate the diagnostic value of measuring the concentration of immunoglobulin free light chains (FLC) in saliva in patients with pSS.Material and methods. The cross-sectional study included 24 patients with pSS over the age of 18 years. PSS was diagnosed according to the 2016 ACR/EULAR classification criteria. The control group consisted of 11 healthy volunteers. Blood-salivary glands histohematic barrier permeability ratio for albumin, FLC was measured. Quantitative determination of FLC and in blood and saliva was performed by enzyme immunoassay. An immunohistochemical study of biopsies of minor salivary glands (MSG) was carried out with a quantitative assessment of CD3+, CD4+, CD8+, CD20+, CD21+, CD68+, CD138+ cells. The Mann–Whitney U-test was used to compare quantitative traits. Identification of diagnostic thresholds for the concentration of FLC in saliva for the diagnosis of pSS was carried out using the ROC analysis method. An operating characteristic curve was plotted, the area under the curve, indicators of diagnostic specificity, diagnostic sensitivity, and diagnostic accuracy were calculated.Results and discussion. The obtained values corresponded to the low permeability of the histohematic barrier of the salivary glands for albumin and FLC in patients with pSS and healthy individuals. The median concentrations of FLC ê and ë in the saliva of patients with pSS and healthy volunteers were 1.08 [0.58; 1.91], 1.038 [0.55; 2.03] mg/l and 0.36 [0.32; 0.54], 0.35 [0.21; 0.52] mg/l, respectively. The concentration of FLC in the saliva of patients with pSS was statistically significantly higher than in the control group (p

Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy have become one of the key approaches in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Evaluation of level of PD-L1 (ligand of the programmed cell death receptor 1) expression on tumor cells using immunohistochemistry is the only approved option for determining the indications of ICIs in this group of patients. However, despite high level of PD-L1 expression, up to 80 % of patients do not respond to therapy due to the presence of primary or acquired resistance, which determines the limited effectiveness of ICI. In addition, 8–17 % of PD-L1-negative patients with NSCLC are also able to respond to ICIs. The limitation of this marker is that it does not allow assessing both intratumoral and systemic immune status. It is necessary to search for additional predictive markers to improve the accuracy of the selection of candidates for immunotherapy, which will avoid costs, wasted time, and a high risk of immune-related adverse events in potentially unresponsive patients. The attention of researchers is devoted to circulating markers in peripheral blood, as a non-invasive alternative to biopsy for predicting and monitoring the response. This review focuses on the most promising immunological markers in peripheral blood as potential predictors of response to ICIs in patients with advanced NSCLC.

Introduction. Urolithiasis is a multifactorial recurrent disease, unevenly spread throughout the world and characterizedby the formation of urinary stones of various chemical compositions, depending on pathogenesis, etiological, and epidemiological risk factors. Understanding the composition of chemicals and their prevailing ratios can help make decisions about treatment tactics, preventive measures to reduce the risk of recurrence and the prevalence of urolithiasis.Purpose of the study. To assess the distribution of chemical components in urinary stones along with an analysis of their population significance.Materials and methods. The urinary stones were obtained from 2854 patients with urolithiasis. The composition of urinary stones was analyzed by using an infrared spectroscopy method.Results. The predominance of oxalate stones was determined in multicomponent kidney stones (83,7%) and the prevalence of urate stones (54,2%) was revealed in monocomponent kidney stones. Urinary stones with a predominance of oxalates contained significantly fewer impurities (12.4%) than urinary stones with a predominance of urates, phosphates and carbonates with an average amount of impurities >24.0%.Conclusion. The analysis of urinary stones distribution based on pathogenic factors showed that the calcium metabolism disturbances prevail in the population of the Russian Federation (88.0%).

Aim. Тo study cardiometabolic factors and the PNPLA3 I148M (rs738409 C>G) gene polymorphism in association with the compensated advanced chronic liver disease (cACLD) in patients with metabolic dysfunction­associated steatotic liver disease (MASLD).Materials and methods. А retrospective cross­sectional study was conducted. The total of 108 patients with MASLD (33 men and 75 women aged 28 to 89 years) involved were divided into two groups based on results of transient elastography: group 1 – with the presence of cACLD (liver stiffness ≥ 8.0 kPa) – 18 patients and group 2 – without cACLD (G) gene polymorphism were studied in both groups. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, and a logistic regression model was constructed for the detection of cACLD.Results. Compared to group 2, patients with cACLD had statistically significant higher prevalence of: arterial hypertension (p < 0.05), type 2 diabetes mellitus (p < 0.01), obesity (p < 0.05), dyslipidemia (p < 0.05), and PNPLA3 gene polymorphism (p < 0.05). The OR for cACLD in individuals with arterial hypertension was 5.58 (95% CI: 1.21– 25.71; p < 0.05), with type 2 diabetes mellitus – 4.58 (95% CI: 1.59–13.21; p < 0.01), with obesity – 3.83 (95% CI: 1.17– 12.52; p < 0.05), with dyslipidemia – 6.12 (95% CI: 1.33–28.20; p < 0.05), in the presence of a polymorphic variant of the PNPLA3 gene in a hetero or homozygous state – 3.9 (95% CI: 1.28–11.89; p < 0.05). The binary logistic regression model for detecting cACLD included type 2 diabetes mellitus, dyslipidemia, and waist circumference. The area under the ROC curve was 0.81 (95% CI: 0.70–0.92), sensitivity was 72.2%, specificity was 74.4%, and accuracy was 84.3%.Conclusion. Type 2 diabetes mellitus, dyslipidemia, and waist circumference are the determining factors for the development of cACLD in patients with MASLD. The PNPLA3 I148M gene polymorphism does not play a leading role in the development of progressive MASLD in the study cohort.

Background. Microsatellites are short tandem nucleotide repeats, the change in length of which plays a key roles in the pathogenesis of various malignant neoplasms. This change is called microsatellite instability. It is caused by aberrations in the genes of DNA mismatch repair system. Tumors with microsatellite instability are a special subtype regardless of location and are characterized by high sensitivity to immune checkpoint inhibitors.Objective – determination of characteristic clinical and morphological patterns of tumors of various localizations with microsatellite instability.Materials and methods. The study included 512 patients with malignant tumors of different localizations. Of these, 359 patients were diagnosed with colorectal cancer, 57 with uterine body cancer, and 57 with stomach cancer. Determination of the status of microsatellite instability was performed by a PCR-based method using 5 mononucleotide markers: BAT-25, BAT-26, NR-21, NR-24, NR-27.Results. The prevalence of microsatellite instability in colorectal cancer, uterine neoplasm and gastric cancer was 6.4; 22.8 and 1.75 %, respectively. Patients with MSI-positive colorectal cancer are characterized by yonger age (p = 0.023), right-sided localization of the tumor (p

Thrombophilia, as well as multiple organ dysfunction, are typical manifestations of the severe new coronavirus infection that closely resemble the clinical signs of catastrophic antiphospholipid syndrome (CAPS). The objective: to assess whether catastrophic antiphospholipid syndrome is an essential manifestation of severe forms of COVID-19.Subjects and methods. 45 patients diagnosed with the new coronavirus infection (SARS-CoV-2) and a severe course of viral pneumonia (more than 3 points on the NEWS score by the admission, CT 3-4, oxygenation index below 100, the need for at least high-flow oxygen therapy). They were assessed for the development of CAPS due to signs of progressing organ dysfunction despite the ongoing intensive therapy, suspected pulmonary embolism and progressing venous thrombosis of a lower extremity or subclavian vein. It was an essential provision that they should have no signs of bacterial infection (blood procalcitonin should be below 0.5 μg/l). The antiphospholipid syndrome was diagnosed based on the detection of antibodies to β-2-glycoprotein in the blood (A/t β-2-GP1 IgGAM, A/t β-2-GP1 IgM, A/t β-2-GP1 IgG) and to cardiolipin (A/t CL IgM , A/t CL IgG) by ELISA tests. The course of the disease was monitored using other routine clinical (temperature, complete blood and urine counts) tests and blood panel tests reflecting the severity of the systemic inflammatory response (ferritin, CRP, interleukins 6 and 18), and the state of the hemostatic, respiratory, circulatory, liver and kidney systems.Results. Antiphospholipid antibodies (aAPL) moderately exceeding the reference values were detected in 9 out of 45 patients (20%), mainly due to IgA and IgM isotypes to β-2-glycoprotein and IgM isotype to cardiolipin. The assessment of the antibody titer in 5 patients over time (after 7 days) revealed a decrease, but it did not affect the outcome (four of them died). In 36 patients, some traces of aAPL were found that did not reach the lower limit of the norm, despite the uniformity of the clinical signs and similarity of biochemical parameters reflecting the severity of organ disorders. The absence of antibodies did not prevent the development of thrombotic complications (thrombosis of large vessels and pulmonary embolism in 5 patients). There were no other manifestations often associated with CAPS (thrombocytopenia, hemolytic anemia, decreased fibrinogen concentration in the blood). Conclusion. Catastrophic antiphospholipid syndrome is not inevitable in severe COVID-19 cases, however, it can develop as one of the manifestations of thrombophilia that occurs in such patients.

IgA anti-CD74 can be a promising marker for diagnosis, assessment of activity and prognosis for ankylosing spondylitis.The aim of the study was to determine the level of IgA anti-CD74 in patients with ankylosing spondylitis and to evaluate its relationships with ankylosing spondylitis activity and carriership of genetic alleles.Materials and methods. In 48 patients with a reliable diagnosis of ankylosing spondylitis, aged 18 to 69 years were measured the ASDAScrp, BASDAI, level of highly sensitive С-reactive protein, concentration of IgA anti-CD74. The polymorphisms of the genes interleukin (IL)-17A197 a/g, IL-17F7 histidine (His) / arginine (Arg), IL-17F11139 c/g, TNF-a-863, TNFα-308, TNFα-238, IL-1B-31, IL- 4-590, IL-6-174, IL-10-1082, IL-10-592, vascular endothelial growth factor (VEGF)-2578, VEGF-936, matrix metalloproteinase (MMP)2-1306, MMP3-5A6A, MMP9-1562, HLA-B27 were evaluated in their relationships with AS activity and IgA anti-CD74 levels.Results. The mean age of patients was 45.1±14.2 years, male - 72.9%, psoriasis - 10.4%, IBD - 2.1%, BASDAI -2.99±0.28, ASDAS - 2.29±0.16, CRP - 6.5±1.65 mg/L, IgA эпй-СВ74 - 18.6±1.73 U/mL (72.9% of the patients with >12 U/mL). The relationship between an increase in concentration of IgA anti-CD74 and ASDAScrp, BASDAI activity indices, between an increase in the level of CRP and the presence of the IL-17A genotype heterozygous for the AA allele (r=0.965) was determined. CRP did not demonstrate the relationship with the BASDAI.An association of IL-17F-11139 СС and the presence of psoriasis (r=0.870) was established. 93.8% of patients with ankylosing spondylitis were carriers of the homozygous histidine allele IL-17F7 (his/his) and the TNF238 allele (GG).Conclusions. The increase in anti-CD74 IgA level was found in 72.9% of patients with ankylosing spondylitis receiving inhibitors of TNF-a and NSAIDs and associated with clinical and laboratory indicators of ankylosing spondylitis activity and with carriage of the homozygous histidine allele IL-17F7 (his/his) detected in 93.8% of patients. Carriage of TNF-238 GG; TNF-863 CC; HLA-B27; TNF-308 GG; IL-4-590 CC; IL-6-174 CG;MMP9-1562 CC; MMP9-1562 CC; VEGF- 936 CC alleles was not associated with an increase in concentration of IgA anti-CD74. CRP demonstrated an association with IL-17A-197 AA (r=0.965) detected in 29.2% of patients with no correlation with the clinical ankylosing spondylitis activity in patients receiving treatment with iTNF-α and NSAIDs.

Antinuclear antibodies (ANAs) represent a spectrum of autoantibodies targeted for various nuclear and cytoplasmic components of the cells. Indirect immunofluorescence assay (IIF) is the main detection method for “antinuclear factor”. A positive ANA test is usually reported as a titer and a pattern of fluorescence. The ANA patterns refers to the distribution of staining produced by antibodies that react with antigens located in nucleus and cytoplasm of HEp-2 cells. To standardize nomenclature and descriptions of the various fluorescence patterns of antinuclear factor (ANF), the Initiative of the International Consensus on ANA Patterns (ICAP) group was developed in 2014. The aim of ICAP is to promote consensus regarding nomenclature of ANA patterns, a microphotograph database, as well as classification depending on the employee skills. Information on the main characteristics, as well as specific clinical associations of the patterns is available at www.ANApatterns.org. In ANA classification trees, the patterns are indicated by the #AC (anticell pattern) alphanumeric code, being divided into nuclear, cytoplasmic and mitotic groups. Depending on the clinical significance and/or ease of recognition, this nomenclature focuses on the differences between the patterns described by specialists at competent and expert levels. Of the nuclear types, the most significant are homogeneous, speckled, dense fine-speckled, centromere, nucleolar, nuclear dots. The cytoplasmic types may be discerned into fibrillar, speckled, mitochondrial, Golgi, rods and rings. On leaders, behalf of the ICAP translation team is headed by the Full Member of Russian Academy of Sciences, Professor A.A. Totolian, under the auspices of the Russian Research Society of Immunologists. In this article, we present the Russianlanguage adaptation of the ICAP nomenclature, in order to ensure unification and standardization of ANA detection results in the patients with autoimmune diseases.

The diagnosis of inflammatory bowel disease (IBD) is based on a combination of clinical, endoscopic, histological, radiological and laboratory methods. However, conventional diagnostic methods are not always sufficiently informative in IBD, especially in the case of unclassified colitis, which necessitates the extension of standard diagnostic approaches. Currently, there is an actively search for non-invasive serological markers for early and differential diagnosis of IBD and for the assessment of activity and prognosis of Crohn's disease (CD) and ulcerative colitis (UC). Among the most interesting serological markers are anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (ANCA), goblet cells antibodies (GAB) and pancreatic autoantibodies (PAB). The aim of this review is to assess the diagnostic and prognostic significance of ASCA, ANCA, GAB, PAB in CD and UC. The paper presents the summary of the data on the role of ASCA, ANCA, GAB and PAB in abnormalities of the immunological tolerance mechanisms to intestinal microflora and intestinal permeability in IBD. We discuss the results of the studies on the associations of ASCA with a complicated CD phenotype, its response to genetically engineered biological therapies, and the need for surgical intervention. The article describes the data on the association of ANCA to the risk of progression of left-sided UC to widespread (total) colon lesions resistant to hormonal therapy, and that of antibodies to DNA-lactoferrin complexes and proteinase 3 to primary sclerosing cholangitis. It has been noted that PAB may be a prognostic marker for ileocolitis, perianal lesions, extraintestinal manifestations and complicated CD, and GAB a predictor of total UC with chronic persistent course. It should be emphasized that combined determination of ASCA, ANCA, GAB and PAB is highly informative, compared to the isolated detection of autoantibodies, for the differential diagnosis and prognosis of CD and UC.

Background. Secondary hemophagocytic lymphohystiocytosis (sHLH) is a hyperinflammatory reaction provoked by some trigger (cancer, autoimmune or infection). The majority of affected patients are at high risk of fatal multiple organ failure without getting immunsupressive treatment.Objective. Clinical and laboratory profile of sHLH patients.Materials and methods. Retrospective study included clinical, instrumental and lab data from the 91 patients followed between June 2009 and June 2019. Diagnosis sHLH had been based on HLH-2004 and H-Score criteria. The analyzed parameters had been fever chart, liver and spleen enlargement, changes in the bone marrow; values levels of glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, bilirubin, triglycerides, total ferritin with percentage of glycosylation. All patients with rheumatic disorders or malignancies had received either immunosuppressive or cytotoxic therapy. Febrile patients received anti-infective treatment according to the local routine protocols.Results. The data from 91 patients (41 male and 50 female) had been analyzed. Median age was 58 (2–90) years. The sHLH trigger-diseases spectrum included leukemia/lymphoma (n = 52), infection diseases (n = 11), autoimmune disorders (n = 5), allogenic bone marrow transplantation (n = 13), unidentified (n = 10). A fever with an unknown origin and refractory to antibacterial treatment had been observed in 87 (96 %) patients. Morphological hemophagocytic evidences in the bone marrow had been found in 83 %. Breath shortening, liver failure, neurologic disturbances, systemic effusions, rash, heart failure had been registered in 83 % patients. Detected splenomegaly presented in 56 %. Laboratory changes, median were as following: serum glutamic-pyruvic transaminase (alanine aminotransferase, SGPT) – 92 (39.2–1060.8) IU/L; serum glutamic oxaloacetic transaminase (aspartate aminotransferase, SGOT) – 105 (40–4177) IU/L; alkaline phosphatase – 225 (120.9–989) IU/L; bilirubin – 50.5 (22–559) µmol/L; triglycerides – 3.2 (1.95–8.6) mmol/L; total ferritin – 10000 (597–255000) ng/mL with glycosylation percentage – 20.45 (0–37.8) %. 71 patients received various of HLH-directed therapy courses. The overall survival rate was 27 %, median follow-up – 540 days.Conclusion. The main clinical and instrumental findings in sHLH are fever, refractory to anti-infective treatment, elevation of transaminases, serum alkaline phosphatase, triglycerides, total ferritine with low glycosylated fraction. Early diagnosing and immunesupression are the main factors of survival.

The article concerns a study of early influence of silicone breast implants on the development of autoimmune reactions and dynamics of prolactin and thyroid hormone levels in women after mammoplasty. At the present time, this issue remains relevant for several reasons: more than 20 million pairs of implants have been installed in the world and the number of their implantations is constantly growing. Despite relative safety of the silicone implants, some of them are periodically banned by regulatory bodies in various countries. At the same time, there is a growing number of controversial publications in the scientific literature, about potential adverse consequences of their use. Some authors suggest an association between the silicone implants and risk of developing autoimmune conditions, connective tissue disorders, and occasional malignancies. On the other hand, the journals are full of publications about the overall safe tolerance of such medical devices by the patients. These considerations served as a pre-requisite to our research. As part of this project, we have assayed serum levels of autoantibodies to ten antigens, as well as contents of prolactin and thyroid hormones by means of ELISA technique in 27 patients before, 3 and 6 months after aesthetic and reconstructive mammoplastics performed within a period of September 2018 to November 2019. As a result, it was found that 5 out of 27 patients exhibited changes in the autoimmunity spectrum and intensity after mammoplasty. In particular, the concentrations of autoantibodies to modified citrullinated vimentin and IgM autoantibodies to cardiolipin exceeded the normal level at 3 and 6 months. In addition, the initially high prolactin concentration in mammoplasty recipients dropped to normal ranges by 3 months after breast surgery, even after several-fold increased initial levels. As for thyroid hormones, there were no statistically significant changes in their dynamics. The increase of autoantibodies to various target antigens after mammoplasty was statistically significant and positively correlated with each other. This can be explained, for example, by dependence on the adjuvant effect of silicone, which is not associated with antigen specificity. However, it may generally stimulate the immune responses.

Objective: to study clinical and laboratory features in patients with anticentromere antibody (ACA)-positive SjЪgren's disease (SD), as well as the sensitivity of different methods for determination of ACA, and to elaborate an algorithm for differential diagnosis in ACA-positive patients.Patients and methods. The V.A. Nasonova Research Institute of Rheumatology followed up 136 patients who were highly positive for ACA. The investigators used the 2001 Russian criteria for the diagnosis for SD; the 2013 ACR/European League Against Rheumatism (EULAR) criteria for that of scleroderma systematica (SDS); the guidelines of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association, and the Russian Society for the Study of the Liver for that of primary biliary cholangitis (PBC)/biliary duct epitheliitis in the presence of SD. Lymphomas were diagnosed by biopsies of affected organs according to the WHO classification. SD was diagnosed in 119 patients; SDS in 49 cases (37 with SDS concurrent with SD and 12 with isolated SDS), PBC/biliary duct epitheliitis in 23 (all cases with PBC/biliary duct epitheliitis concurrent with SD and/or SDS); 5 patients were excluded from the investigation. Further analysis included 131 ACA-positive patients. The patients were divided into three groups: SD (n=82 or 62.6%); SD+SDS (n=37 or 28.24%); SDS (n=12 or 9.16%).Results and discussion. Autoantibodies to centromere peptide (CENP) A and CENP-B in the same titers were detected in all ACA-positive patients, regardless of diagnosis. Comparative analysis of three patient groups revealed no statistically significant differences in the frequency of laboratory deviations. The signs characteristic of classical SD (rheumatoid factor (RF)), anti-Ro and anti-La antibodies, leukopenia, higher ESR values, hypergammaglobulinemia, and elevated IgG/IgA levels) were found in a small proportion of patients. The frequency and severity of glandular manifestations did not differ in SD and SD + SDS. PBC/biliary duct epitheliitis was present in 17.5% of ACA-positive patients (in most antimitochondrial antibody-positive cases); no statistically significant differences in its frequency were found between the groups. Other extraglandular manifestations in SD and SD + SDS were identified in a smaller number of patients. All sclerodermic spectrum manifestations were more common in SD and SD + SDS than in BS. Pulmonary arterial hypertension was not diagnosed in any patient from the SD group. MALT lymphomas were detected in 19 ACA-positive patients. Those were present only in BS patients and absent in the SDS group. MALT lymphomas developed in the first 10 years after the onset of SD. The transformation of MALT lymphoma into diffuse large B-cell lymphoma was observed in 2 patients. The main signs of lymphomas in SD patients were persistent parotid salivary gland enlargement, decreased levels of complement C4 and peripheral blood CD19+ cells, as well as cryoglobulinemic vasculitis, serum monoclonal secretion, lymphoid infiltration in the minor salivary glands (a focus score of >4), and severe damage to the salivary and lacrimal glands.Conclusion. ACA-associated SD is an independent disease subtype characterized by an increased risk for SDS, PBC, and MALT lymphomas and by a low frequency of the systemic manifestations and laboratory signs characteristic of classical SD. Regardless of the detected type of antibodies and the presence or absence of extraglandular manifestations, damage to the salivary and lacrimal glands progresses in SD, which often leads to lymphomas; therefore, the therapy that may prevent this complication should be initiated as soon as possible after SD diagnosis. The lymphoproliferation signs identified in this investigation should be taken into account in all ACA-positive patients with SD for the early diagnosis of lymphoid tumors before therapy is prescribed. An algorithm for differential diagnosis in seropositivity for ACA is presented. Determination of autoantibodies to CENP-A and CENP-B does not allow the differential diagnosis in ACA-positive patients.

The article presents the analyzes of literature sources describing the relationship between pathological alleles of some genes and prostate cancer, which can be used to determine the risk of developing prostate cancer. Mutations of the genes such as HOXB13 (251G/A, G84E), BRCA1 (5382insC, 185delAG, 4153delA, 3819delGTAAA, 3875delGTCT, 300T/G,2080delA) and BRCA2,CHEK2 (1100delC, I157T), ELAC2 (Leu217, Thr541, 650T, 1618a), cdh1 gene (160C/a), AR gene (CAG trinucleotide repeats), VDR gene (rs1544410, rs10875692, rs7301552, rs7975232, rs731236), GST family genes (null alleles of GSTM1 and GSTT1, single-nucleotide substitutions of GSTP1 313a/G and 341c/T), as well as Bloom's syndrome genes were studied. We described what mutations have a proven statistical association with an increased risk of prostate cancer. At the same time, the correlation between the patient's ethnicity and an increased risk of prostate cancer, when there are mutations of BRCA1, AR, VDR and GST family genes, is also noted.

Aim. In this study we evaluated clinical effectiveness and safety of nebulized prostacyclin in patients with Novel Coronavirus Disease (SARS-CoV-2). Materials and methods: We have included 44 male patients with moderate PCR confirmed SARS-CoV-2 infection in this study. Control group consisted of 23 patients treated with nebulized prostacyclin (PGI2). besides standard therapy. We compared intensiveness and duration of infectious intoxication syndrome, duration of fever, cough as well as SpO2 level, complete blood count and chemokine status values. Results: Statistically significant difference in duration of fever, cough, intensiveness and duration of infectious intoxication syndrome were observed. Lymphocyte and platelet counts were significantly higher in control group We have also noticed significantly lower level of proinflammatory mediators and C4-complement component in control group. Only 1 adverse effect associated with inhaled prostacyclin was reported. Conclusion. Nebulized prostacyclin showed therapeutic efficacy and good safety profile in adults with moderate COVID-19.

The case of chronic hepatitis C 1b genotype with grade 3 fibrosis according to Metavir, complicated by the development of mixed type III cryoglobulinemia, cryoglobulinemic vasculitis with damage to the skin vessels of the skin (hemorrhagic vasculitis), and the liver (alternatively proliferative vasculitis) is demonstrated. The introduction of daclatasvir + asunaprevir was virologically unsuccessful: mutations D168E and L31V were detected against the background of a virological breakthrough. A repeated course of antiviral therapy with the combination of Grazoprevir + Elbasvir in combination with sofosbuvir led to a stable virologic response, partial immunological and clinical remission.

Idiopathic recurrent pericarditis (IRP) and adult-onset Still's disease (AOSD) are polygenic autoinflammatory diseases, in the pathogenesis of which pro-inflammatory cytokines from the interleukin-1 superfamily play a central role.Aim. To compare serum concentrations of proinflammatory cytokines and glycosylated ferritin (GF) in patients with IRP and AOSD during an exacerbation.Material and methods. The study included 15 patients with AOSD, 15 — IRP. The diagnosis of AOSD was established using the Yamaguchi criteria (1992). IRP was diagnosed in accordance with the 2015 European Society of Cardiology on the diagnosis and management of pericardial diseases. Blood sampling from all patients was carried out during the recurrence period prior to the anti-inflammatory therapy initiation. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), procalcitonin, total ferritin and GF was assessed. The results obtained were compared with levels of biochemical parameters, high-sensitivity C-reactive protein (CRP), as well as with white blood cell (WBC) and neutrophil counts.Results. The median age in the AOSD group was 28 years, and the IRP — 55 years. An increase WBC count >10*109/L was detected in 10 and 9 patients in the AOSD and IRP groups, respectively. The concentration of CRP was increased in all patients and did not differ in the study groups (p=0,836).The highest values of ferritin and GF levels were found in the AOSD group (1416 ng/ml vs 408 ng/ml, p=0,008) and (12% vs 33,9%, p=0,067), respectively. In both groups, increased concentrations of IL-6 and IL-18 were determined. In the AOSD group, the concentration of IL-18 was higher than in the IRP group (2114 pg/ml vs 161,5 pg/ml, p

Multiple sclerosis is chronic demyelinating disease of the central nervous system with autoimmune inflammation and accretive neurodegeneration. One of the characteristics of autoimmune inflammation in multiple sclerosis is a polyspecific intrathecal humoral immune response against neurotropic viruses (Measles, Rubella and varicella Zoster) called MRZ-reaction. This immune response is based on polyclonal activation of mature B lymphocytes in the central nervous system and intrathecal synthesis of antibodies to anamnestic antigens unrelated to viral replication in the central nervous system as well as serum antibody release. Immunoglobulins produced against neurotropic viruses are an integral part of the oligoclonal antibody pool in the cerebrospinal fluid. Because immunoglobulins can penetrate the blood brain barrier, not only serum and cerebrospinal fluid specific antibody indices are calculated, but also blood-brain barrier antibody permeability (Qalbumin, QIgG) are taken into account to assess their intrathecal synthesis. The aim of the study was to assess the informative value of the intrathecal antibodies against neurotropic viruses (MRZ-reaction) in multiple sclerosis. There were enrolled 60 patients divided into 2 groups: group 1 — 35 patients diagnosed with multiple sclerosis, group 2 — 25 patients with inflammatory and non-inflammatory disоrders of the central nervous system. Paired cerebrospinal fluid and serum samples were collected from all patients to measure level of oligoclonal IgG, immunoglobulin free kappa and lambda light chains, IgG index and specific antibodies indices, followed by assessing magnitude of MRZ-reaction. We found that the MRZ-reaction was the most specific test to diagnose multiple sclerosis. Intrathecally produced antibodies against neurotropic viruses were detected in 3 of 35 multiple sclerosis patients with lacking oligoclonal IgG antibodies. In addition, a relationship between MRZ-reaction and degree of EDSS disability was found in MS patients: peak EDSS score was reported in patients with intrathecally synthesized antibodies against 3 viral agents, whereas the minimum EDSS score — among MRZ-negative patients. Thus, assessing MRZ-reaction seems rational for confirming MS diagnosis in case of other negative laboratory tests (oligoclonal immunoglobulins and free kappa/lambda light chains in cerebrospinal fluid) allowing to improves diagnostic accuracy and evaluation of MS severity.

Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases.

Diagnosis of neuromuscular diseases is complicated by the variety of clinical manifestations and requires the use of additional methods, an important place among which is the pathomorphological study of skeletal muscle biopsy. Despite the fact that the procedure for taking a muscle biopsy is not technically difficult, to obtain informative material a multitude of conditions must be observed at the stages of pre-analytical processing of the obtained tissue samples. Violation of the technology of taking, storing and fixing the material contributes to the formation of artifacts that limit the possibilities for further analysis of the morphological changes in tissue biopsy. A comparison was made of the effectiveness of various methods for cryoprocessing of muscle tissue samples and the manufacture of histological specimens with a subsequent assessment of morphological changes. As a result, the main causes of artifacts were identified. The optimal method for processing muscle biopsy specimens is indicated, which makes it possible to prevent the appearance of artifacts as much as possible and to ensure the preservation of tissue for research.

The aim of the study was to evaluate clinical, immunologic and anti-viral efficacy of antiviral therapy (АVT) with drugs of the direct antiviral action (DAA) of the chronic hepatitis C (CHC) complicated with secondary mixed cryoglobulinemia in small cohort of patients. Patients and methods: The cohort consisted of 12 patients with CHC (without signs of a coinfection of HIV, a hepatitis B virus) complicated with mixed cryoglobulinemia (criocrit more than 5% and presence of cryoglobulinemia-related symptoms). Standard DAA based therapy was indicated in all patients: 2 cases daclatasvir and asunaprevir, 3 cases daclatasvir and sofosbuvir and 7 cases Dasabuvir;Ombitasvir+Paritaprevir+Ritonavir. Results: Anti-viral response at 12 and 24 weeks was found in 91,6% (11/12) treated patients. In one case (on the daclatasvir and asunaprevir) resistance to both drugs developed. Clinical response was confirmed in 83% – 10/12 (25% – the complete response, 58% – the partial response). Despite of anti-viral response kidney damage persisted in 2 patients without apparent improvement. There was one lethal outcome at 25th week since the beginning of treatment because of bilateral pneumonia and thromboembolism in patient with kidney involvement treated with steroids and cytostatics. In 25% of patients total elimination of cryoglobulins was confirmed by the end of AVT and in 75% dramatic decrease of criocrit was found. Conclusion: We confirmed good virologic, clinical and immunologic response and safety of AVT with DDA in patients with HCV induced crioglobulinemia, especially when using schemes with a high genetic barrier (daclatasvir and sofosbuvir, Dasabuvir;Ombitasvir+Paritaprevir+Ritonavir).

We described a case of amyotrophic lateral sclerosis (ALS) with comorbid HIV infection. The diagnosis was confirmed by genetic tests. The difficulty of the differential diagnosis between amyotrophic lateral sclerosis and HIV-associated ALS syndrome is discussed.

The review presents the data available in the literature on the use of the lupus band test (LBT) for systemic lupus erythematosus (SLE). LBT is a direct immunofluorescence method used to detect immunoglobulins and complement factors in the dermoepidermal junction of skin biopsy specimens. LBT may be applied as one of the diagnostic tests for early diagnosis of SLE in patients without skin manifestations and in those of incomplete SLE. Like the results of other laboratory tests, those of LBT may be taken into account when establishing a final diagnosis only in conjunction with other clinical, immunological and instrumental data.

The article describes the clinical case when malignant hyperthermia was diagnosed in the patients during the cardiac surgery. The patient had anesthesia with desflurane. The state of the patient was stabilized due to timely diagnostics and aggressive therapy with non-specific agents and cardiopulmonary bypass. The article presents different variants of clinical manifestations of this complication, ways of diagnostics and specific therapy.

Biological preparations (BP) obtained by gene engineering possess a special characteristic called immunogenicity, i.e. propensity of biological drugs to induce an undesired immune response associated with arising anti-drug antibodies. These antibodies can change BP pharmacokinetics and pharmacodynamics, and therapeutical efficacy. A significant proportion of hemodialysis patients with end-stage renal disease treated by recombinant erythropoietin (rEPO) have clinical features of resistance to such therapy. The aim of the study was to investigate whether anti-rEPO antibodies are associated with hemoglobin concentrations (Hb) and red blood cells counts (RBC) in hemodialysis patients, receiving long-term rEPO therapy. This research was performed at the Research Institute of Nephrology at the First St. Petersburg I.Pavlov State Medical University. Thirty-seven hemodialysis patients (pts) with end-stage renal disease and anemia treated with different rEPO formulations were included into the study. The patients were further divided into two groups: those with diminished and normal clinical response to rEPO therapy (DCR, n = 21 vs NCR group, n = 16, respectively). To determine threshold levels of antibodies to rEPO-beta (Roche, Switzerland) we tested blood serum samples of 35 healthy blood donors who never received rEPO in the past. Concentration of antibodies was measured by means of dot-blot method. The threshold antibody concentrations were defined by measurement of anti-rEPO concentrations in 2-fold stepwise dilutions (1:10 to 1:200) of blood sera from 35 healthy donors .The threshold value for rEPO-binding antibodies was 20.27 µg/ml (95 CI%±0.43). Antibodies to rEPO were found in 54 % of serum samples in the patients. Anti-rEPO antibodies concentrations correlated with mean values of hemoglobin and erythrocyte counts over a period of 12-months for the entire group of hemodialysis patients (r = -0.368, p = 0.025 and r = -0.336, p = 0.042 respectively). Concentration of anti-rEPO antibodies, and the mean weekly rEPO dose were significantly higher in DCR group, compared to NCR group (p = 0.0019). In conclusion, higher levels of anti-rEPO binding antibodies seem to be associated with decreased therapeutic response to the clinically applied rEPO formulations.

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease (ARD) associated with the production of broad-spectrum antibodies, the detection of which is of important diagnostic and prognostic values. The problems of RA diagnosis are associated with the limited sensitivity of currently used serological markers.Objective: to evaluate the diagnostic informative value of autoantibodies against different post-translationally modified (PTM) vimentin peptides in patients with RA and other ARDs.Patients and methods. The frequency of autoantibodies against different isoforms of vimentin was estimated in 144 patients with RA, in 36 patients with other ARDs (ankylosing spondylitis and scleroderma systematica), and in 25 patients of a control group, who had no rheumatic diseases. Antibodies against different PTM vimentin peptides obtained using citrullination, carbamylation/homocitrullination, and acetylation were determined. Anti-citrullinated vimentin (anti-CitVim) peptide, anti-carbamylated vimentin (anti-CarVim) peptide, and anti-acetylated vimentin (anti-AcVim) peptide autoantibodies of IgG and IgA classes were estimated in the serum by enzyme immunoassay.Results. The results of the study showed that IgG and IgA anti-CitVim had the maximum area under the ROC curve (AUC) (0.859 and 0.855, respectively). A slightly smaller AUC was seen in IgG anti-CarVim (0.85), IgG anti-AcVim (0.784), and IgA anti-AcVim (0.651). The diagnostic sensitivity and diagnostic specificity were 66.2 and 96.77% for IgG anti-CitVim, 60.56 and 91.94% for IgA anti-CitVim, 91.55 and 53.23% for IgG anti-CarVim, 63.38 and 93.55% for IgG anti-AcVim, and 49.3 and 70.97%, IgA anti-AcVim, respectively. Positivity for IgG anti-CitVim, IgG anti-CarVim, and IgG anti-AcVim, and anti-IgA CitVim was significantly more frequently detected in patients with RA than in those with other ARDs and in the control group (p

OBJECTIVE. The authors evaluated the role of antibodies to striated muscle and acetylcholine receptors in diagnostics of myasthenia gravis and thymoma, as well as outcomes of thymectomy and prognosis of myasthenia course. MATERIAL AND METHODS. The study investigated correlations of antibody content to striated muscles and acetylcholine receptors from the presence and size of thymoma, myasthenia in 157 patients with various pathologies of the thymus. The dynamics of antibody concentrations was followed up after thymectomy. RESULTS. Antibody titer to striated muscle depended on the presence and size of thymoma, severity of myasthenia and changed after thymectomy. Concentration of antibodies was associated with the presence of thymoma and it didn’t change after surgical treatment. Thymoma wasn’t revealed in patients who were seronegative to both antibodies. CONCLUSIONS. Seropositivity according to one of antibody could indicate the presence of thymoma, but its absence to both antibodies allowed doctors to eliminate this diagnosis. Antibodies to acetylcholine receptors are important markers of myasthenia. Monitoring of antibody titer dynamics to striated muscles after thymectomy could be useful for assessment of response to surgical treatment and prognosis of course of myasthenia.

Distinct changes of B-cell subpopulations are observed in most systemic rheumatic diseases associated with polyclonal B cell hyperreactivity. Immunosuppressive and cytostatic therapy may also differentially influence B lymphocyte subsets in these. We studied subpopulations of B cells in systemic rheumatic patients along treatment with cytostatics. We analyzed B cell phenotypes in ninety-nine blood samples from the patients with systemic lupus erythematosus (SLE, n = 25), systemic sclerosis (n = 27), Sjogren’s syndrome (n = 47) in the course of their hospital treatment. Control group consisted of 49 healthy blood donors. Phenotyping of blood B-cell subpopulations was performed by means of flow cytometry (Beckman Coulter, USA). Naïve B-cell subpopulations in SLE patients who underwent cyclophosphan treatment, were underrepresented, if compared with normal control group, whereas plasmablast levels were increased irrespectively of medication mode. B cell population exhibits a natural heterogeneity, thus making it necessary to analyze distinct B cell subpopulations as independent functional units, when studying different rheumatic diseases. The levels of plasmablasts which are active antibody producers, remain high, despite immunosuppressive therapy performed in SLE. Thus, therapy targeted against certain B cell subsets, could be able to provide a more effective treatment for the patients with systemic rheumatic diseases.

Anti-heterogeneous nuclear ribonucleoprotein (RNP) autoantibodies (AAbs) are encountered in many autoimmune rheumatic diseases (ARDs). The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjö gren's syndrome (SS) and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6%) and 8/53 (13%) patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144) of the patients with RA; 40.3% (23/57) of those with AS, in 67.5% (27/40) of those with SSc, in 36.4% (16/44) of those with SLE, and in 13.3% (2/15) of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml), but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA.

α1-Antitrypsin (α1-AT) deficiency is a common genetic disorder characterized by low serum α1-AT levels and a clinical manifestation of pulmonary emphysema and liver disease. In addition to its classical manifestations, α1-AT deficiency frequently accompanies granulomatosis with polyangiitis (GPA); in this case the role of α1-AT deficiency in the clinical course of GPA has not been defined. Objective: to estimate the prevalence of pathological α1-AT phenotypes in GPA and other systemic vasculitides (SV) and to determinate their impact on the clinical course of GPA. Subjects and methods. The investigation enrolled 86 patients with SV, including GPA (n=47), microscopic polyangiitis (MPA) (n=16), eosinophilic granulomatosis with polyangiitis (EGPA) (n=12), and polyarteritis nodosa (PAN) (n=11). A control group included 46 healthy donors. Isoelectric focusing was used to phenotype α1-AT in blood samples and its concentrations were determined. The phenotypes of α1-AT were compared with the overall SV activity index using the Birmingham Vasculitis Activity Score (BVAS), the vasculitis damage index (VDI), the nature of an organ lesion, and the markers of immune inflammation (proteinase 3-antineutrophil cytoplasmic antibodies, total IgG, and C3 and C4 fractions of the complement system). Results and discussion. Pathological α1-AT phenotypes were detected in 17% (8/47) of the patients with GPA, 6.25% (1/16) of those with MPA and absent in EGPA and PAN. Patients with GPA had PiZZ (n=1), PiMZ (n=4), PiMF (n=2), and PiMS (n=1) phenotypes; those with MPA had a PiMS-phenotype. The detection of a pathological α1-AT phenotype in patients with GPA was characterized by the high values of BVAS and VDI (p

Serial immunological and neurologic evaluation, and testing forinfections was performed in 32 patients (m 23, f 9, 1458years) with chronic non-inflammatory unconscious states. Themain group of patients (n=18) received treatment for subclinicalinfections and other infectious agents revealed. Treatment in thecontrol group (n=14) was targeted only on community-acquiredand nosocomial microbiota. Markers of inflammatory intrathecalresponce of the central nervous system (CNS) were found in 88%(28/32) patients, and this was associated with Chlamydia spp. incerebrospinal fluid (CSF) and/or blood (р0.01). Markers ofvarious mmunopathological vasculites/vasсulopathies wererevealed in 84% patients (27/32), and the tendency of their interrelationwith Chlamydia spp. in comparison with other subclinicalinfections was found. In some cases clinical data was confirmedby autopsy results. In the main group of patients during treatmentwe found the changes of structure of immunopathological syndromeand appearance in the CSF and/or blood of previouslyundiagnosed subclinical infections with further sanation of latentinflammatory process. It was accompanied by neurophysiologicalsigns of disbalance of a stable pathological condition withimprovement of brain metabolism according to PET data. In thecontrol group the specified changes were not found, and theshort-term and long-term results of treatment were worse. Theobtained data showed that in patients with chronic non-inflammatoryunconscious states in the substance and in the vessels ofbrain develops latent inflammatory process with immunopathologicalcomponent associated with Chlamydia spp. and other subclinicalinfections. It appears to be the factor of additional braindamage that consolidates the pathological condition in CNS. Itis reasonable to consider this process during elaboration of tacticsof treatment for these patients.

Testing for IgG+IgM autoantibodies to gangliosides of peripheralnerves (asialo-GM1, GM1, GM2, GD1a, GD1a, GD1b, GQ1b)was performed in 95 patients with GuillainBarr syndrome (GBS)in Moscow. In 70 patients (74%) acute inflammatory demyelinatingpolyneuropathy (AIDP) was diagnosed, and in 25 patients (26%) either acute motor axonal neuropathy (AMAN) or acute motorsensoryneuropathy (AMSAN). The role of antibodies to gangliosidesfor prognosis of the disease course and response to pathogenictreatment was assessed. Antibodies to gangliosides were found in55 patients (57.9%) more often in patients with AMAN/AMSAN(p0.05). The whole range of antibodies was found both in patientswith AIDP and AMAN/AMSAN. Anti-GM1 were found in bothsubtypes of GBS. Anti-GD1b were associated withAMAN/AMSAN (p0.05). There was a correlation between anti-GM1 and diarrhea (p0.05), anti-asialo-GM1 and campylobacteriosis(p0.05). There wasnt found significant correlation betweenanti-GD1 and axonal subtypes, diarrhea in anamnesis, and campylobacteriosis.Association of severe GBS and elderly age, camplylobacteriosisand axonal subtypes was confirmed. AMAN/AMSANsubtypes, severity of the disease, necessity in mechanical ventilationwere characterized by insufficient efficacy of pathogenic therapy.The same factors and elderly age were associated with unfavorableprognosis in terms of absence of unassisted walking in 6 and12months. Anti-GD1a were associated with sever course of the disease,including necessity in mechanical ventilation. Immunologicfactors are not sufficient in prognosis of the treatment efficacy.Antibodies to GM1 were associated with unfavorable prognosis withabsence of unassisted walking in 6 months. Clinical and neurophysiologicaldata is crucial for making diagnosis and prognosisof the GBS course. Testing for autoantibodies to gangliosidescould be helpful in diagnostics of GBS. It is possible to use thattest for revealing axonal type of the disease (anti-GD1b), prognosticationof severe course of GBS (anti-GD1a) and unfavorablerehabilitation of unassisted walking.

Chronic obstructive pulmonary disease (COPD) is one of the leading reasons of mortality in the whole world. The insufficiency of alpha-1-antitrypsin (А1АТ) protein is an important factor of genetic predisposition to COPD development. А1АТ deficit can be diagnosed with the help of phenotyping. Detection of PiZZ phenotype of А1АТ preconditions 95% of А1АТ deficit cases whereas PiMM phenotype testifies about the conservation function of the protein. Detection of A1AT in case of COPD might be accompanied by a graver course of the diseases, it is characterized by peculiarities of complex study parameters of the external respiratory function and densitometric values of the pulmonary tissue determined by computer tomography.The objective of this study is comparison of external respiratory function in COPD patients with PiZZ and PiMM phenotype of А1АТ.Materials and methods: COPD patients with PiZZ phenotype of А1АТ (N = 6) and PiMM phenotype of A1AT (N = 75) were studies. The following spirometric values were evaluate: forced expiratory volume per 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, maximum expiratory flow rate (MEFR), peak flow rates (PFR50 and PFR75), mean flow rate (MFR), as well as the total lung capacity (TLC) etc. Spiral computer tomography was performed with application of the densitometric analysis software.Evaluation of the intensity of dyspnoe and effect of symptoms on the quality of life was done.Results. Comparison of spirometric values showed that for patients at PiZZ phenotype of А1АТ showed lower values of FEV1/ FVC, PFR50, PFR75, MFR, DLco, va and higher parameters of MEFR, FVC and TLC than in PiMM phenotype of А1АТ (p < 0,05*).Conclusions: in COPD patients with PiZZ phenotype of А1АТ more intense deviations of bronchial obstruction, reduction of elastic properties of the pulmonary tissues, hyperinflation, reduction of the capillary bed due to emphysematous pulmonary involvement are observed.

Alpha-1-antitrypsin (A1AT) exerts a wide spectrum of protective effects, being focused on reduction of secondary injury in inflammation. Moreover, A1AT inhibits some serine proteases, and down-regulates production of proinflammatory cytokines. A number of known A1AT phenotypes is accompanied by affection of cytokine profile in inflammatory processes, thus increasing the risk of disorders associated with A1AT deficiency.The aim of our study was to evaluate cytokine profiles in the patients with different A1AT phenotypes. Were collected eighty-six blood sera from the persons with suspected A1AT deficiency. The A1AT phenotypes and concentrations were determined in these samples. The patients were divided into four groups, depending on their A1AT variants, i.e., PiMM, PiZZ, PiMZ and rare A1AT phenotypes. The serum levels of IFNγ, TNFα, IL-6, IL-8, and IL-17 were measured in these groups by means of ELISA technique.The mean levels of IL-6 comprised 73.52±4.363 pg/ml in the patients with PiZZ phenotype, being higher than in cases of PiMM phenotype (45.61±8.01 pg/ml, p < 0.05). The IL-17 levels were also found to be increased in the groups with PiZZ and PiMZ phenotypes, as compared with PiMM phenotype (p < 0.001). The mean IL-17 values in the samples with PiZZ, PiMZ, and PiMM phenotypes were 80.13±13.56 pg/ml, 106.7±26.28 pg/ml and 42.73±18.52 pg/ml, respectively. Meanwhile, there were no significant differences in IL-8, IFNγ and TNFα levels among different A1AT phenotypes. The results of this study let us conclude that the cytokine imbalance may be crucial to onset of diseases associated with A1AT deficiency.

The study was conducted to evaluate the activity parameters of local and systemic inflammation in women suffering from bronchial asthma (BA). 119 women with asthma were studied, and 48 with a regular menstrual cycle and 71 in menopause; 38,7% of BA was mild, 61,3% – moderate severity. All patients were examined in the remission phase of the disease. On the background of normal values of conventional indicators of inflammation it was showed a significant increase of IL 1 alpha and IL 8 more in the group of women with regular menstrual cycles and normal body weight, IL1 alpha amounted to 489±80 pg/ml and IL8 – 631±122 pg/ml (p