Background. IIron deficiency (nonanemic iron deficiency and iron-deficiency anemia) remains the most common condition in the general clinical practice. Iron deficiency negatively affects the prognosis of the underlying disease and reduces the quality of patient’s life. One of the most common and difficult-to-diagnose cause of iron deficiency in clinical practice is autoimmune gastritis.Objective. The aim of the study was to determine the incidence of iron deficiency (nonanemic iron deficiency and iron-deficiency anemia) in patients with autoimmune gastritis and to identify the factors contributing to its development.Material and methods. Sixty-two patients previously diagnosed with autoimmune gastritis were included in a cohort observational study. The mean age of patients was 53.5 ± 12.6 years (from 25 to 79 years). By gender, there were predominantly females – 52 (83.9%), and 10 (16.1%) males. All patients underwent laboratory tests: complete blood count, iron metabolism parameters (ferritin, serum iron), antiparietal cell antibodies, anti-intrinsic factor antibodies, serological biomarkers of gastric atrophy.Results. According to the patients’ history data and laboratory tests, iron deficiency was determined in 38 (61.3%) patients. At the time of inclusion to the study, iron-deficiency anemia was found in 7 (11.3%), anemia of complex etiology (iron deficiency and vitamin B12 deficiency) – in 2 (3.2%), nonanemic iron deficiency (ferritin < 30 μg/l) – in 8 (12.9%) patients. According to the hemoglobin level anemia grade was mild in the majority of patients – 21 (70.0%), moderate – in 6 (20.0%), severe – in 3 (10.0%) patients. The time period between iron-deficiency anemia detection and diagnosing of autoimmune gastritis ranged from several months to 25 years, with average mean 48.7 months (SD = 67.39). The frequency of iron deficiency among females and males was different –67.3% and 30.0%, respectively (χ2 = 4.92, p = 0.027; OR = 4,08 [95% CI 1.103-20.923]). Iron deficiency was more common among women of reproductive age then among menopausal women (80.0% vs 29.6%, χ2 = 13.252, p < 0.001; OR = 9,5 [95% CI 2,637-34,227]). Serological biomarkers of gastric atrophy (pepsinogen I < 30 μg/L, pepsinogen I/pepsinogen II ratio < 3.0) were detected more frequently in patients with iron deficiency than in patients without them (89.5% vs 58.3%, χ2 = 8.160, p = 0.005; OR = 6.071 [95% CI 1.628-22.638]). Iron deficiency was detected in all patients with hypothyroidism, while in patients with euthyroidism it was less common (100% vs 36.8%, χ2 = 7.287, p = 0.007). Oral iron supplements were noneffective in 60.5% of patients and were associated with adverse events in 23.7% of patients.Conclusion. Autoimmune gastritis should be included in the differential diagnosis of iron deficiency of unknown etiology, especially in cases of refractoriness to oral iron supplements. Nonanemic iron deficiency and iron-deficiency anemia in autoimmune gastritis develop primarily due to a decrease in acid production and proteolytic activity of the stomach, and additional factors include female gender, reproductive age, and hypothyroidism.

Aim: to investigate the clinical and laboratory patterns of SLE and to evaluate the risk of steroid resistance (SR) in patients with upregulated IS gene expression. Patients and Methods: data from 19 female patients with SLE, aged 18–45 years, were analyzed. The expression levels of type I interferon (IFN) genes (IFI27, IFI44L, IFIT1, ISG15, SIGLEC1, ACTB) were determined by real-time PCR, with calculation of the cumulative expression score, the IS. Clinical and laboratory manifestations of SLE were compared between subjects with normal and elevated IS. The risk of SR was estimated using an original methodology based on a purpose-designed algorithm and computer software. Results: patients with serositis exhibited more frequent upregulation of IFIT1 expression (3 of 4 patients with serositis versus 3 of 15 without serositis, p=0.05) and IFI44L expression (3 of 4 with serositis versus 2 of 15 without serositis, p=0.04). Patients with antiphospholipid syndrome (APS) demonstrated more frequent overexpression of IFIT1 (4 of 5 with APS versus 3 of 14 without APS, p=0.05) and SIGLEC1 (5 of 5 with APS versus 5 of 14 without APS, p=0.02). Patients with a high IS had higher antinuclear antibody (ANA) titers at disease onset (Me [Q1; Q3] 1:1440 [1:280; 1:7040] versus 1:640 [1:320; 1:960], p=0.02), elevated serum uric acid (UA) levels (407.3±147.9 μmol/L versus 346.2±86.5 μmol/L, p=0.04), and higher total cholesterol concentrations (5.74±1.2 mmol/L versus 4.35±0.9 mmol/L, p=0.05) compared with patients with a normal IS. Patients with a high IS were more likely to be at risk of developing steroid resistance (4 of 8 versus 1 of 11 patients, respectively, p=0.05). Conclusion: patients with a high IS, compared with those with a normal IS, more frequently exhibit greater immunological activity at disease onset, along with higher serum UA and cholesterol levels. Upregulated expression of individual IS genes was more prevalent in patients with juvenile-onset disease, serositis, and APS than in patients without these manifestations. KEYWORDS: systemic lupus erythematosus, interferon signature, hyperuricemia, cardiovascular risk, serositis, antiphospholipid syndrome, steroid resistance. FOR CITATION: Musiychuk M.M., Aliev D.B., Lapin S.V., Nazarov V.D., Devyatkina E.A., Inamova O.V., Gaydukova I.Z. Clinical and immunological features of systemic lupus erythematosus in patients with upregulated interferon signature gene expression. Russian Medical Inquiry. 2026;10(3):160–167 (in Russ.). DOI: 10.32364/2587-6821-2026-10-3-8

Aim. To study serum lipoprotein(a) (Lp(a)) levels in the general population of the Russian Federation (RF) from various federal districts and to assess the prevalence of elevated Lp(a) levels corresponding to cardiovascular risk (CVR) categories. Material and methods. This retrospective analysis of serum Lp(a) levels was performed in the laboratories of OOO Helix (2021-2024, n=14625) and OOO Invitro (2023-2024, n=23485). A total of 38110 test results in the general population of the Russian Federation were processed. The median age was 49 years (39; 60). The Lp(a) level was determined in two units of measurement: molar — nmol/L (Helix) and mass — g/L (Invitro). Values higher than or equal to 105 nmol/L or 0,5 g/L were considered elevated in serum Lp(a). CVR categories taking into account blood Lp(a) levels were stratified according to the 2023 European Society of Cardiology (ESC) guidelines. Data analysis was conducted across Russian Federation federal districts based on the sex and age of the subjects. Results. A combined analysis of data from two large laboratories representing all Russian showed that, according to the 2023 ESC CVR stratification based on Lp(a) levels, low CVR was detected in 74,9% of subjects, intermediate CVR in 6,7%, moderate CVR in 6,5%, high CVR in 3,9%, very high CVR in 7,5%, and extremely high CVR in 0,5%. Thus, every fifth Russian resident tested had a Lp(a) level ≥0,5 g/L or ≥105 nmol/L, corresponding to moderate or higher CVD. The highest number of individuals with moderate (0,5-0,69 g/L, 105-174 nmol/L), very high (0,9-1,79 g/L, 190-429 nmol/L), and extremely high (≥1,8 g/L, ≥430 nmol/L) CVR was found in the Southern Federal District. The highest proportion of individuals with high CVR (0,7-0,89 g/L, 175-189 nmol/L) were found in the Siberian Federal District. Women had significantly higher Lp(a) levels than men (p=0,001). A moderate increase in blood Lp(a) concentrations with age was observed. Conclusion. The analysis results have important epidemiological significance and demonstrate a high prevalence of increased risk of atherosclerotic cardiovascular disease (ASCVD) associated with elevated blood Lp(a) levels. Variability in Lp(a) levels was identified across different Russian regions, as well as sex and age differences. The results can be used to develop ASCVD screening and prevention strategies.

Background: serological profiling of inflammatory bowel diseases (IBD) using autoantibodies represents an additional non-invasive tool for differential diagnosis and prognosis of the clinical course of Crohn’s disease (CD) and ulcerative colitis (UC). Aim: to determine the frequency, diagnostic and prognostic significance of pancreatic autoantibodies (PAB), autoantibodies to glycoprotein 2 (GP2) and intestinal goblet cells antibodies (GAB) in assessing the clinical outcomes of CD and UC. Materials and methods: the study included 117 patients with CD, 45 with UC and 24 with IBD unclassified (IBDU). The comparison group consisted of 36 patients with other gastrointestinal diseases (irritable bowel syndrome with diarrhea (IBS-D), celiac disease, autoimmune gastritis (AIH)), the control group consisted of 29 conditionally healthy individuals. The content of PAB and GAB class IgG was measured by the IIF method (EUROIMMUN AG, Germany), GP2 classes IgA and IgG and fecal calprotectin (FCP) – by the ELISA method (Generic Assays GmbH, Germany, BÜHLMANN Laboratories AG, Switzerland). Results: the frequency of PAB IgG, GP2 IgA and GP2 IgG in patients with CD was 25.6%, 24% and 12%, respectively, which was significantly higher compared to patients with UC (6.6%, 15.5% and 4.4%), IBDU (4.1%, 12.5% and 0%), AIH (5.2%, 0% and 5.2%), IBS-D (0%, 0% and 0%) and the control group (6.9%, 3.4% and 6.9%) (p<0.05), while it did not differ from patients with celiac disease (9%, 18.2% and 9%). Combined determination of PAB IgG+ and/or GP2 IgA+/G+ has the highest predictive value in the differential diagnosis of CD from UC using the cutt-off value of GP2 IgG at ≥5.0 U/ml (sensitivity – 47%, specificity – 87%, AUC (95% CI): 0.64 (0.55–0.73), p<0.05). Seropositivity for PABs correlates with the level of FCP in CD, and also serves as an unfavorable prognostic marker of severe exacerbation, complicated form and the need for surgical treatment of CD. The incidence of GAB IgG in patients with CD was 21.3% vs. with UC – 35.5% (p = 0.2), IBDU – 25% (p = 0.9) and celiac disease – 9% (p = 0.4), while it was seronegative in patients with IBS-D, AIH and the control group. Determination of GAB IgG has a good predictive value in the diagnosis of UC, especially in combination with a seronegative result of determining PABs (sensitivity – 32%, specificity – 91.1% (AUC (95% CI) = 0.62 (0.54–0.69), p = 0.002), and can also serve as an additional marker of terminal ileitis and the need for surgical treatment of CD. Conclusion: serological examination of IBD with combined determination of PAB IgG, GP2 IgA, GP2 IgG and GAB IgG allows to increase the efficiency of differential diagnostics and prediction of individual course of CD and UC.

Background. Expansion-based autosomal dominant spinocerebellar ataxias (ADSСA-E) represent a clinically and genetically heterogeneous group of inherited neurodegenerative disorders characterized by cerebellar atrophy. According to global population data, they account for approximately 61 % of all autosomal dominant spinocerebellar ataxias. The number of nucleotide repeats is a key determinant of penetrance, expressivity, and age of onset, necessitating precise molecular genetic analysis. Significant differences in the structure of ADSСA-E across populations underscore the need for regional studies. Aim. Analysis of the molecular structure and frequency of ADSCA-E in a sample of Russian patients with cerebellar ataxias. Materials and methods. DNA samples from 1272 patients with clinical signs of ataxia (2017–2024) were analyzed. The number of repeats in the ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATXN10, PPP2R2B, NOP56, and ATXN8OS genes was determined using fluorescent polymerase chain reaction and fragment analysis. The age at referral to the laboratory was considered an indirect marker of disease aggressiveness. Statistical analysis was performed using GraphPad Prism 10. Differences were considered statistically significant at p 0.05. Pearson’ correlation coefficient was used to calculate correlation. Results. A pathological expansion was identified in 102 (8 %) patients. The most frequent form was spinocerebellar ataxia (SCA) type 1 (62.7 %), followed by SCA type 2 (17.6 %), SCA type 3 (5.9 %), and SCA type 6 (3.9 %); other types were rare. A case of combined SCA type 1 and SCA type 8 mutations was recorded in one patient. For SCA type 1 and SCA type 2, a significant negative correlation was established between the expansion size and the age at referral (p 0.0001; r = –0.6839 and –0.8838, respectively). Conclusion. Data on the frequency and spectrum of ADSCA-E in the Russian Federation, including rare forms, were obtained. The prognostic significance of the repeat number was confirmed, and the necessity of molecular genetic testing, taking into account regional disease prevalence patterns, was emphasized.

Background. In the last decade, the understanding of the pathogenesis of autoimmune hepatitis (AIH) has significantly deepened, based on the results of new clinical studies some diagnostic issues have been revised and immunosuppressive therapy regimens have been optimized.Materials and methods. The latest Russian clinical guidelines for the diagnosis and treatment of AIH were presented in 2013; and in 2017, the first Russian agreement on the diagnosis and treatment of AIH was held. Updating approaches to the management of patients with AIH necessitated next systematization for use in clinical practice. In February 2024, the final session was held to discuss the provisions of the second agreement on the diagnosis and treatment of AIH.Results. This publication presents the main discussion points of the agreement regarding methods and algorithms for detecting autoantibodies, the role of liver biopsy, revised morphological criteria for AIH, optimized immunosuppressive therapy regimens, updated criteria for assessing the response to therapy.Conclusions. The agreement was the result of the work of a group of experts on the diagnosis and treatment of AIH and represents the basis for the creation of updated federal clinical guidelines.

The Objective was to study changes in serum C-reactive protein (CRP) concentration in the postoperative period in patients with Crohn’s disease (CD), as well as to substantiate and develop an algorithm for using predictors of inflammation to prevent the possible development of postoperative complications. Methods and materials. In 62 patients, who underwent surgical interventions performed for CD complications, CRP parameters was studied daily during the first seven days and on the twelfth day of the postoperative period. Results. In 27.4 % of cases in the postoperative period, CD patients showed activation of the immune-inflammatory process, which increased the risk of postoperative complications. The threshold values of CRP were determined, which can serve as predictors of the activation of immune-inflammatory processes in the early postoperative period in Crohn’s disease. Conclusion. A pathological increase in CRP on the 3–4th day after surgery should be considered as a predictor of activation of immune-inflammatory processes and as an indication for therapeutic correction.

Инфекция, вызванная вирусом Эпштейна—Барр (ВЭБ), протекает благоприятно, за исключением редких форм, к которым относятся хроническая активная болезнь (ВЭБ-ХАБ) и вторичный гемофагоцитарный синдром (ВЭБ-ВГФС). ВГФС — это угрожающее жизни состояние, связанное с тяжелым нарушением регуляции иммунного ответа. В основе патогенеза лежит активация цитотоксических Т-лимфоцитов, NK-клеток и макрофагов с гиперпродукцией провоспалительных цитокинов и развитием неэффективного системного воспалительного ответа. Типичные проявления — устойчивая фебрильная лихорадка, умеренная цитопения, цитолитический и холестатический синдромы, полиорганная недостаточность. К наиболее эффективным средствам купирования гиперергической реакции относится этопозид. В работе представлены результаты лечения 5 пациентов с ВЭБ-ВГФС и 1 — с ВЭБ-ХАБ. У всех больных отмечалась лихорадка, печеночная дисфункция, гипофибриногенемия и цитопения. При ВГФС присутствовала также выраженная гиперферритинемия. Ко времени подготовки публикации 3 пациента оставались под наблюдением без признаков болезни.

Introduction. Spondyloarthritis (SpA) associated with inflammatory bowel disease (IBD) is a disease in the SpA group developing in patients with Crohn’s disease (CD) and ulcerative colitis. Gut-vascular barrier impairments, including increased epithelial permeability and endothelial glycocalyx (EGc) damage, have been demonstrated in both CD and axial SpA (axSpA), and can serve as a pathogenetic basis for the joint development and progression of these diseases.Aim. To evaluate the significance of EGc damage and epithelial permeability markers in patients with CD-associated axSpA.Materials and methods. We examined 22 patients with axSpA associated with CD (group A), 29 patients with axSpA without IBD (group B), 27 patients with CD (group C) and 28 conditionally healthy controls (group D). Calprotectin (FC) and zonulin (FZ) in feces, hyaluronan and syndecan 1 in serum were studied. Perfusion boundary region (PBR) and the Microvascular Health Index (MVHS) were measured by dark-field microscopy in the sublingual region.Results. In patients with CD-associated axSpA, an increase in PBR (p<0.001) and a decrease in MVHS (p=0.001) were revealed in comparison with healthy individuals. Only CD patients revealed decreased serum hyaluronan (p=0.006) associated with colitis and deep ulcers on endoscopy. Increased PBR allowed to identify very high axSpA activity in group A with a sensitivity of 100 % and specificity of 83.3 %. In group A patients, a correlation between hyaluronan and FC was found (ρ=–0.541; p=0.030). A classification tree, including FC, FZ, hyaluronan, and MVHS, was constructed to determine the presence of CD in axSpA patients with an accuracy of 90.2 %.Conclusions. The study of the gut-vascular barrier damage markers allows to improve the methods of diagnosis and assessment of the integral activity of axSpA associated with CD.

Обоснование. Сердечно-сосудистые заболевания (CCЗ) атеросклеротического генеза являются ведущей причиной смертности во всем мире. Наиболее распространенным наследственным нарушением липидного обмена, характеризующимся повышением концентрации холестерина липопротеинов низкой плотности и преждевременным развитием сердечно-сосудистых заболеваний атеросклеротического генеза, является семейная гиперхолестеринемия. Цель. Изучить биохимические и молекулярно-генетические особенности пациентов очень высокого сердечно-сосудистого риска с подозрением на семейную гиперхолестеринемию и оценить параметры чувствительности и специфичности биохимических показателей липидного профиля. Материалы и методы. Исследование включало 50 пациентов очень высокого сердечно-сосудистого риска в возрасте от 18 до 55 лет с уровнем ХС ЛПНП более 4,0 ммоль/л. Всем пациентам были проведены электрофорез липидов, определение аполипопротеинов и молекулярно-генетические исследования в лаборатории диагностики аутоиммунных заболеваний при Научно-методическом центре Минздрава России по молекулярной медицине ПСПбГМУ имени академика И.П.Павлова. Результаты. Согласно результатам NGS-секвенирования в исследуемой группе патогенные варианты в генах LDLR и АРОВ были обнаружены в 10% и 4 % случаев, соответственно. MLPA анализ для определения протяженных делеций и дупликаций гена LDLR не выявил структурных изменений. Наиболее высокой прогностической ценностью обладал биохимический показатель аполипопротеин В100. Заключение. Дальнейшее исследование молекулярно-генетических и биохимических особенностей позволит персонализировать тактику ведения пациентов с семейной гиперхолестеринемией.

Beta-thalassemia being one of the most widespread monogenic diseases in the world is characterized by the HBB gene mutations leading to beta-globin chain decrease. Despite of the specific laboratory features diagnosis of beta-thalassemia may seem difficult especially when speaking of minor forms and carriers. The common diagnostic standard includes complete blood count with analysis of hematological indices, iron deficiency exclusion and examination of hemoglobin fractions. The last and the crucial step is providing molecular-genetic study of HBB gene as the method allowing to verify the diagnosis. The beta-thalassemia pathogenesis, comprehensive genetic classification and various laboratory diagnostics tools are discussed in this review. There exists huge knowledge about beta-thalassemia prevalence in endemic regions but little is known of beta-thalassemia incidence in nonendemic countries, e.g., Russian Federation. Nevertheless, studying beta-thalassemia prevalence in Russia remains relevant considering multi ethnicity of Russian Federation. This review presents the diagnostics algorithm with the use of HBB gene Sanger sequencing and the results of beta-thalassemia prevalence pilot research. According to the data obtained the minimal possible beta-thalassemia incidence in Moscow accounts for 0.16 %.

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<0.05). Seropositivity for ANCA IgG in patients with UC was 54 %, which is significantly higher than in patients with CD, IBDU, AIG – 9.9 %, 9.5 % and 5.3 %, respectively (p<0.05). In patients with IBS-D and the control group, ASCA IgA and IgG and ANCA IgG were not detected. The combination of ASCA IgA and/or IgG seropositivity with a negative ANCA IgG result is more sensitive in differentiating CD from UC than the isolated determination of ASCA IgA (39.5 % vs. 25.3 %) with a specificity of 95.8 % and 96.5 %, respectively. The sensitivity of the combined detection of ANCA IgG with negative ASCA IgA and IgG results was comparable to the isolated detection of ANCA IgG – 52.5 % vs. 53.8 %, while the specificity increased to 94.6 %. ASCA IgA/G seropositivity serves as an unfavorable prognostic marker for the onset of CD before the age of 40, the stenotic and penetrating behavior, as well as the need for surgical treatment of the disease. Higher ANCA IgG titers were observed in patients with severe attack of UC (320 [320;640]) compared to mild attack (40 [40;80], p<0.05).Conclusion. ASCA and ANCA are highly specific markers of CD and UC, the combined determination of which makes it possible to increase the efficiency of serological examination not only in differential diagnosis, but also in personalized prediction of the clinical course of IBD.

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. Hemophagocytic syndrome (HPS) is a reaction of severe, excessive, but ineffective inflammation. HPS is divided into primary or as a complication of a different causes — secondary HPS (sHPS).Aim: to analyze the effi cacy of different treatments in sHPS patients.Materials and methods. For the retrospective analysis, the medical documentation of patients who were treated in the period from June 2009 to January 2023 was used. The H-Score and HLH-2004 criteria were used to verify sHPS. The results of clinical blood analysis and biochemical tests are presented. The survival was analyzed within two weeks after the verification of sHPS. The main treatment options for sHPS were etoposide, glucocorticosteroids (GCSs), anticancer therapy and intravenous immunoglobulin.Results. The study included data from 130 patients, median age 56 years (18–90); 70 females and 60 males with sHPS. All patients received treatment with a drug change in cases of inefficiency: a total of 186 episodes. A stable response was achieved in 74 (56.9 %) patients. The median survival in patients without a response was 2 days. If the therapy was effective, the median survival was not reached. Positive dynamics were observed during the first day after the start of effective treatment, however, a few patients had transient worsening of some markers. The main factor in the negative prognosis was the degree of multiple organ failure during sHPS verification. In the group of patients with autoimmune diseases, GCSs were the most effective, with a response reached in 75 % of cases. For patients with resistance, as well as in patients with Epstein—Barr virus infection and blood malignancy, etoposide proved to be effective in 65.7 % of cases.Conclusion. sHPS was accompanied by an increase in pancytopenia, cytolytic, cholestatic syndromes, hypocoagulation, azotemia, hypertriglyceridemia and excessive hyperferritinemia. After the initiation of effective therapy, persistent clinical and laboratory responses developed during the first day. Therapy by GCSs was effective in most patients with autoimmune diseases associated with sHPS. With other forms of sHPS in the studied group, etoposide had the most pronounced effect.

Introduction. Hemophagocytic syndrome (HPS) is a reaction of severe, excessive, but ineffective inflammation. HPS is divided into primary or as a complication of a different causes - secondary HPS (sHPS). Aim: to analyze the efficacy of different treatments in sHPS patients. Materials and methods. For the retrospective analysis, the medical documentation of patients who were treated in the period from June 2009 to January 2023 was used. The H-Score and HLH-2004 criteria were used to verify sHPS. The results of clinical blood analysis and biochemical tests are presented. The survival was analyzed within two weeks after the verification of sHPS. The main treatment options for sHPS were etoposide, glucocorticosteroids (GCSs), anticancer therapy and intravenous immunoglobulin. Results. The study included data from 130 patients, median age 56 years (18-90); 70 females and 60 males with sHPS. All patients received treatment with a drug change in cases of inefficiency: a total of 186 episodes. A stable response was achieved in 74 (56.9 %) patients. The median survival in patients without a response was 2 days. If the therapy was effective, the median survival was not reached. Positive dynamics were observed during the first day after the start of effective treatment, however, a few patients had transient worsening of some markers. The main factor in the negative prognosis was the degree of multiple organ failure during sHPS verification. In the group of patients with autoimmune diseases, GCSs were the most effective, with a response reached in 75 % of cases. For patients with resistance, as well as in patients with Epstein-Barr virus infection and blood malignancy, etoposide proved to be effective in 65.7 % of cases. Conclusion. sHPS was accompanied by an increase in pancytopenia, cytolytic, cholestatic syndromes, hypocoagulation, azotemia, hypertriglyceridemia and excessive hyperferritinemia. After the initiation of effective therapy, persistent clinical and laboratory responses developed during the first day. Therapy by GCSs was effective in most patients with autoimmune diseases associated with sHPS. With other forms of sHPS in the studied group, etoposide had the most pronounced effect.

Background. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by loss of motor neurons. The cause of neurodegeneration is predominantly a homozygous deletion of the SMN1 gene, leading to a decrease in the synthesis of the SMN protein. The clinical picture of the disease is heterogeneous and varies depending on the age of onset and the ability to perform motor functions. Several genetic and molecular modifiers have been identified that are thought to influence the severity of SMA. One of the most proven factors is the number of copies of the SMN2 gene.Aim. Description of quantitative and structural features of the SMN1 and SMN2 genes in patients with SMA 5q.Materials and methods. The study included DNA samples from patients examined for the number of copies of the SMN1 and SMN2 genes at the Scientific and Methodological Center for Molecular Medicine, I.P. Pavlov First Saint Petersburg State Medical University, for the period from 2021 to 2022. Gene copy numbers were determined by multiplex ligation-dependent probe amplification using the SALSA MLPA P021 SMA kit (MRC Holland). We assessed an indirect parameter of aggressiveness (the age of the patient’s visit to the laboratory) to assess the severity of clinical manifestations of SMA. Statistical analysis was carried out using the statistical data processing program GraphPad Prism9.Results. A statistically significant direct correlation was found when studying the relationship between the number of copies of the SMN2 gene and the age of molecular diagnosis (r = 0.3960, p <0.0001). An assessment of the significance of differences between individual groups of patients gave a statistically significant result: <0.0001 when comparing groups of patients with 2 and 3 copies; <0.0001 – with 2 and 4 copies; 0.0370 – with 3 and 4 copies. 9 % of patients had a hybrid SMN1/SMN2 structure. Therefore, the significance of differences between the age of molecular diagnosis of patients with homozygous deletion of SMN1 and the age of molecular diagnosis of patients with the hybrid SMN1/SMN2 gene between groups with the same number of copies of the SMN2 gene was assessed. A statistically significant result (p = 0.0070) was found between patients with SMN1 deletion + 2 copies of SMN2 and patients with the hybrid gene SMN1/SMN2 + 2 copies of SMN2.Conclusion. The number of SMN2 gene copies correlates with the age of molecular diagnosis and indirectly predicts the age of SMA onset. The effect of the SMN1/SMN2 hybrid gene on the age of molecular diagnosis of SMA was comparable to the effect of the regular SMN2 gene.

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<0.05).Conclusions. The absolute and relative number of peripheral blood Tc subsets is altered in SLE patients compared with the control group. It was found that patients with SLE contained increased number of Tc2 cells, which seems to be associated with markers of disease activity. These results demonstrate a prominent pathological role of Tc2 in SLE. While Tc1, Tc17, Tc17.1, Tfc subsets probably have regulatory functions