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.

Introduction. In severe cases of coronavirus disease 2019 (COVID-19) pulmonary infiltration is accompanied by cytokine storm syndrome (CSS) development. Besides COVID-19, CSS can be triggered by the range of pathologies, which include hemophagocytic lymphohistiocytosis (sHLH) and septic shock (SS). The aim of this study was to compare immunological profiles in fatal cases of COVID-19, sHLH and SS. Material and methods. Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17A, IL-18, IFN-γ, TNF-α, procalcitonin, neopterin, ferritin with percent of glycosylated fraction (% GF) were measured in 37 COVID-19 fatal cases, collected during 2020 year prospectively;and in 39 sHLH and 47 SS fatal cases, collected within 2018–2019 years retrospectively. Comparison groups also included 194 non-fatal COVID-19 cases and 20 healthy donors, collected during 2020 year. Cytokine concentrations, procalcitonin and neopterin were measured by enzyme-linked immunosorbent assay;the ferritin level was determined by the turbidimetry method. The percent of glycosylated ferritin fraction (% GF) was calculated by the modified method of M. Worwood et al. Results. Deceased patients with COVID-19 had higher IL-6, IL-8, IL-10, IL-18, procalcitonin median levels compared to the survived. Meanwhile IL-8, IL-18, IFN-γ, TNFα and ferritin concentrations were significantly lower in deceased COVID-19 patients compared to sHLH and SS. The levels of IL-6 and procalcitonin in fatal COVID-19 were comparable to SS, but significantly higher than in sHLH. Leucocytes were higher in COVID-19 compared to both SS and sHLH. Conclusion. Each fatal condition was accompanied by specific features of the cytokine profile: high IL-6 combined with low IFN-γ, TNFα in COVID-19;high IL-8, IL-6 with low IL-17A, IL-2 in SS;high IL-18, ferritin, IFN-γ with low IL-6, procalcitonin, % GF in sHLH.

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. Secondary hemophagocytic syndrome (SHPS) is a reaction of systemic hyperinflammation triggered by infectious, tumor, or autoimmune processes. With no immunosuppressive (modulating) therapy most patients die from multiple organ failure. Aim. To describe organ lesions characteristic of SHPS patients. Materials & Methods. The retrospective study included patients treated from June 2009 to June 2019. SHPS was diagnosed using HLH-2004 criteria and H-Score. The analysis focused on the incidence and character of lesions in lungs, central nervous system, liver, skin, and cardiovascular system. All patients with persistent fever received anti-infective treatment with broad-spectrum antibiotics in line with local hospital practice. Patients with collagenosis and tumors, which caused SHPS, received standard immunosuppressive and antitumor therapy, respectively. Results. The analysis covered the data of 91 patients (41 man and 50 women), median age was 58 years (range 2-90 years). SHPS was caused by hematological malignancies (n = 52; 57 %), infections (n = 11; 12 %), autoimmune diseases (n = 5; 6 %), and allogeneic hematopoietic stem cell transplantation (n = 13; 14 %). In 10 (11 %) patients no cause was identified. Immunosuppressive therapy was administered to 71 (78 %) patients. Overall survival was 27 % (median 15 days) with median follow-up for alive of 540 days (range from 7 days to 10 years). Clinically significant organ lesions were identified in 76 (83 %) patients. Most commonly SHPS was reported together with polyserositis, respiratory and hepatic disorders, and neurological symptoms from focal deficit to seizure status. Less often skin lesions (from macular rash to epidermolysis bullosa) and such cardiovascular disorders as arrhythmia and/or arterial hypotension were observed. The effective SHPS therapy resulted in restoration of organ functions. Conclusion. SHPS can cause respiratory disorders, polyserositis, different neurological disorders, cytopenia in patients with unexplained fever and cytolytic and/or cholestatic syndrome. Primary organ lesions as well as clinical and laboratory manifestations of SHPS may vary in different patients.

Sarcoidosis and tuberculosis have many clinical and laboratory similarities, which allowed researchers to assume the presence of common pathogenetic mechanisms in the development of both diseases. Recently, much attention has been paid to investigate the autoimmune origins in these pathologies. The aim of this study is to find out the characteristics of the autoinflammatory immune response in sarcoidosis and tuberculosis. In patients with sarcoidosis (n = 93), tuberculosis (n = 28), and in healthy donors (n = 40), the serum anti-MCV concentration was measured by ELISA, and B cell subpopulations were analyzed by flow cytometry. Based on the results obtained, the formula ([B-naïve%]\[B-memory%]) * ([B-CD38%] + [B-CD5%]) / [anti-MCV] was described. The increase in the calculated index by more than 5 units with a sensitivity of 80.00% and a specificity of 93.10% (AUC = 0.926) suggest the presence of the autoimmune component, which is more typical for sarcoidosis, rather than tuberculosis patients and may serve as a diagnostic criterion.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often complicated by cytokine storm syndrome. Although many interleukins (IL) have predictive value, the sensitivity and specificity of a single marker is limited. AIM: The purpose of the study is to develop an objective and informative cytokine storm scale for assessing the risk of developing a critical course in patients with COVID-19 associated pneumonia. MATERIALS AND METHODS: A total of 226 cases of COVID-19 were investigated, 36 (16 %) of which were with poor outcomes. The cytokines IL-1b, IL-2, IL-6, IL-8, IL-10, IL-18, TNF-, IFN, IFN- were studied by enzyme immunoassay, commercial kits manufactured by Vector-Best, RF. RESULTS: Since IL-6, IL-10, IL-18, and procalcitonin were associated with disease severity and death, these indicators were integrated into a 12-point scale called the cytokine storm scale. The patients who scored more than 6 points had a high risk of a poor outcome of the disease. According to ROC analysis, the area under the curve for the cytokine storm scale was larger than for each of the four markers separately [AUC 0.90 (95% CI 0.84550.9592), p 0.001]. CONCLUSIONS: Thus, the cytokine storm scale system presents superior performance in determining patients with favorable and fatal outcomes to each individual cytokine.

The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10% to 15% of patients are cured by the procedure. Preclinical studies indicate that substitution of post-transplantation cyclophosphamide with bendamustine (PTB) in a prophylaxis regimen may be associated with an augmented graft-versus-leukemia (GVL) reaction. The aim of this study was to establish the optimal dose of PTB and evaluate the antileukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. In the prospective trial (NCT02799147), PTB was administered in doses of 140, 100, and 70 mg/m2 on days +3 and +4. Myeloablative conditioning with fludarabine and oral busulfan was provided to all patients. The first 12 patients received single-agent PTB, and subsequent patients received combination therapy with tacrolimus and mycophenolate mofetil (MMF). Inclusion criteria were acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to at least one induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. The study cohort comprised 22 patients with AML and 5 with ALL. Seven patients were enrolled in the 140 mg/m2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m2 and 70 mg/m2 groups. Primary refractory disease was documented in 41% of the patients, and secondary refractory was documented in 59%. The median blast count in the bone marrow at the start of the conditioning was 18% (range, 6% to 97%). Transplantation was performed with a matched sibling donor in 5 patients, a matched or mismatched unrelated donor in 15, and a haploidentical donor in 7. Engraftment was documented in 93% of the patients, including 89% with complete remission and 63% without measurable residual disease. After PTB prophylaxis, we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3 to 5 CRS in 44%. The most frequent clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation in 37%, and central nervous system toxicity in 26%. The development of CRS was associated with use of an HLA-mismatched donor (75% versus 20%; P = .0043). Classic acute GVHD was documented in 44% of the patients. Grade II-IV acute GVHD was associated with grade 3 to 5 CRS (67% versus 25%; P = .031). Moderate and severe chronic GVHD in the 100-day survivors were more often observed after single-agent PTB than after the combination immunosuppression (100% versus 18%; P = .002). A relatively low relapse rate was observed for this patient population. Three-year overall survival was 28% (95% confidence interval [CI], 13% to 46%), and event-free survival was 29% (95% CI, 13% to 46%). Nonrelapse mortality was 46% (95% CI, 25% to 64%), and the cumulative incidence of relapse was 26% (95% CI, 11% to 44%). No relapses were documented after day +100. There were no statistically significant differences among the dose groups (P = .3481); however, survival was higher in the 100 mg/kg group. Survival was higher in patients with AML compared with those with ALL (35% versus 0%; P = .0157). PTB represents a promising option to augment the GVL effect in refractory AML; however, the high CRS-associated mortality necessitates additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications, at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation.

The level of beta-catenin reflects the activity of the WNT/β-catenin signaling pathway involved in the development of alveolitis with the fibrosis formation, the marker of which is periostin (P). Aim: To investigate the level of beta-catenin (BC) and P in the blood with various HRCT patterns of EIP and IIP. Materials and methods: 50 patients - EIP (20 men, 30 women, mean age 57.1±1.0 years) with HRCT patterns of NSIP (eNSIP, 39/50), UIP (eUIP, 11/50) and 34 patients with IIP (14 men, 20 women, mean age 60.5±1.9 years) with HRCT patterns of NSIP (iNSIP, 12/34), UIP (iUIP, 22/34) were investigated. The levels of BC and P were determined by the enzyme immunoassay method. Results: During exacerbation BC blood level was significantly higher in patients iNSIP (p<0.001) and iUIP (p<0.1), vs eNSIP and eUIP. The level of P at iUNP, vs eUIP, was also significantly higher, regardless of the phase of the disease. BC level in the exacerbation was higher than in remission (p<0.2) only in patients with eUIP. High level of P was revealed in NSIP remission, in comparison to exacerbation (p<0.02), that may be associated with the fibrotic NSIP formation. ВС blood level in NSIP was significantly higher than in UIP, both in exacerbation (eNSIP, p<0.2) and in remission (iNSIP, p<0.1; eNSIP, p<0.005). In remission of iNSIP and eNSIP also significantly higher P levels were revealed vs remission iUIP (p<0.05) and eUIP (p<0.02). Conclusion: BC reflects the activity of the pathological process, which is much more pronounced in IIP than in EIP. High levels of P in NSIP indicate the fibrotic NSIP development and the advisability of antifibrotic therapy.

1 St. Petersburg State University, 7–9, Universitetskaya nab., St. Petersburg, 199034, Russian Federation 2 St. Petersburg Research Institute of Phthisiopulmonology, Health Ministry of Russia, 2–4, Ligovskiy pr., St. Petersburg, 191036, Russian Federation 3 Pavlov First St. Petersburg State Medical University, 6–8, ul. L'va Tolstogo, St. Petersburg, 197022, Russian Federation 4 Federal Almazov North-West Medical Research Centre, 2, ul. Akkuratova, St. Petersburg, 197341, Russian Federation

Chronic obstructive pulmonary disease (COPD) is multifactorial disease, which is characterized by airflow limitation and can be provoked by genetic factors, including carriage of the PiZ allele of the protease inhibitor (Pi) gene, encoding alpha-1 antitrypsin (A1AT). Both homozygous and heterozygous PiZ allele carriers can develop COPD. It was found recently that normal A1AT regulates cytokine levels, including IL-17, which is involved in COPD progression. The aim of this study was to determine whether homozygous or heterozygous PiZ allele carriage leads to elevated level of IL-17 and other proinflammatory cytokines in COPD patients. Materials and Methods. Serum samples and clinical data were obtained from 44 COPD patients, who included 6 PiZZ, 8 PiMZ, and 30 PiMM A1AT phenotype carriers. Serum concentrations of IL-17, IL-6, IL-8, IFN-γ, and TNF-α were measured by the enzyme-linked immunosorbent assay (ELISA). All A1AT phenotypes were verified by narrow pH range isoelectrofocusing with selective A1AT staining. A turbidimetric method was used for quantitative A1AT measurements. Results. COPD patients with both PiZZ and PiMZ phenotypes demonstrated elevated IL-17 and decreased IFN-γ levels in comparison to patients with the PiMM phenotype of A1AT. Thereafter, the ratio IL-17/IFN-γ in PiZZ and PiMZ groups greatly exceeded the values of the PiMM group. Homozygous PiZ allele carriers also had significantly higher levels of IL-6 and lower levels of IL-8, and IL-6 values correlated negatively with A1AT concentrations. Conclusions. The presence of the PiZ allele in both homozygous and heterozygous states is associated with altered serum cytokine levels, including elevated IL-17, IL-17/IFN-γ ratio, and IL-6 (only PiZZ), but lower IFN-γ and IL-8.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III–IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57–89%) in acute GVHD and 81% (95% CI 67–92%) in chronic. Overall survival was 59% (95% CI 49–74%) in acute group and 85% (95% CI 70–93%). The major risk factors for lower survival were grade III–IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III–IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

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 investigation of biomarkers for fibrosis and lung tissue damage is very important for the diagnosis and prognosis of interstitial lung disease, as well as treatment strategies. The biomarkers secreted by Type II pneumocytes and cells of the bronchiolar epithelium are most reflective of the formation of pulmonary fibrosis and the degree of damage to the lung tissue. The levels of Krebs von den Lungen-6 (KL-6), alveolomucin (mucin-antigen 3EG5), and Clara cell secretory protein in occupational interstitial lung diseases (e.g., exogenous alveolitis, pneumoconiosis), caused by exposure to organic and inorganic factors, were analysed in dependence of disease activity phase. The level of alveolomucin in pneumoconiosis and in occupational alveolitis remission may reflect the extent of pulmonary fibrosis, which is a prognostic sign of the outcome of the disease. Higher specificity and lower sensitivity of alveolomucin compared to KL-6 can be used as a screening test for exogenous alveolitis. KL-6 and alveolomucin are more useful biomarkers than Clara cell secretory protein for diagnosis, exacerbation, and progression of occupational alveolitis.

Introduction. The basis of autoimmune inflammation in multiple sclerosis (MS) is the polyclonal activation of B lymphocytes in the central nervous system, followed by intrathecal immunoglobulin production, caused by the synthesis of antibodies to measles, rubella, and varicella zoster viruses (MRZ reaction). The study aimed to assess the possibility of using the IgG index, oligoclonal immunoglobulin synthesis, the permeability coefficient of the blood-brain barrier, specific indices of antibodies against measles, rubella, and varicella zoster viruses with the calculation of the MRZ reaction in the diagnosis of MS, neuromyelitis optica, and acute disseminated encephalomyelitis. Materials and methods. The study included 40 patients with the following diagnoses: MS (n = 19), acute disseminated encephalomyelitis (n = 11), and neuromyelitis optica (n = 10). Intrathecal synthesis indicators were measured in all patients in paired samples of cerebrospinal fluid and serum. Study results. In the study group, the MRZ reaction was a specific test for the diagnosis of MS and was not found in neuromyelitis optica or acute disseminated encephalomyelitis. An increase in the IgG synthesis index was observed in only 90.5% of patients with MS, and oligoclonal IgG was detected in only 71.4% of cases. Elevated albumin quotient values are not typical for MS, which characterizes the degree of permeability of the blood-brain barrier. Conclusion. The MRZ reaction is a highly specific laboratory marker for verifying MS. It also enables differential diagnosis of MS and other demyelinating diseases.

Take-Home Message. This study provides a new diagnostic index based on the antibodies to mutated citrullinated vimentin concentration and the level of different B subsets. Determination of index over 5 Units proved to be characteristic of sarcoidosis, what might help to differentiate SD from TB. Abstract. In some cases there is a problem of differential diagnosis of sarcoidosis(SD) and tuberculosis(TB)because of the similarities in clinical, X-ray and laboratory features. The aim of this study was to search for new differential diagnostic criteria for sarcoidosis and tuberculosis by calculating the index, based on the level of autoantibodies to modified citrullinated vimentin (anti-MCV) and the level of B-cell subpopulations. These parameters were measured in patients with sarcoidosis (n = 93), tuberculosis (n = 40) and healthy donors (n = 40) using the ELISA and cytometry. The absence of a statistically significant difference when comparing the level of anti-MCV, the number of B-cells in SD and TB suggests that these changes may be characteristic of granulomatous diseases. The use of the formula Ds=([B-naïve%]\[B-memory%])*([B-CD38%]+[B-CD5%])/[anti-MCV] might allow to differentiate SD with an increase in the calculated index of more than 5 units with a sensitivity of 80.00% and specificity of 93.10% (AUC = 0.926).