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Acute disseminated encephalomyelitis (AEM) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS), usually single-phase. In WREM, multiple lesions of the central nervous system of an inflammatory-demyelinating nature accompanied by extremely polymorphic neurological disorders develop acutely or subacutely. The review considers the issues of epidemiology, trigger factors of the inflammatory process, clinical manifestations, differential and molecular diagnostics of WECM, and outlines the ways for further study of this pathology.

Introduction: To identify novel velocity waveform parameters of the ophthalmic artery and central retinal artery by computer-aided image processing of Doppler ultrasonography measurements, and to evaluate correlations between the waveform parameters and different demographics and disease severity of open-angle glaucoma patients., Methods: Thirty-six images of 36 open-angle glaucoma patients were considered. A semiautomated image processing code was used to detect the digitalized ophthalmic artery and central retinal artery velocity waveforms and to extract the waveform parameters. Concordance correlation coefficient, two-sample t-test, and Pearson's correlation coefficient were used to test for similarities, differences, and associations among variables., Results: Female glaucoma patients showed a statistically higher ophthalmic artery normalized distance between ascending and descending limb (p = 0.004), hypertensive glaucoma patients a statistically higher ophthalmic artery peak systolic velocity time (p = 0.025), glaucoma patients with hyperlipidemia a statistically higher ophthalmic artery resistivity index (p = 0.023) and a statistically higher ophthalmic artery peak systolic velocity acceleration (p = 0.025), glaucoma patients with cardiovascular diseases a statistically lower central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.033) and a statistically higher central retinal artery period (p = 0.028), and patients with different body mass index a statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.016). Groups with different disease severity, classified following the Brusini glaucoma staging system 2, showed statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p < 0.001) and central retinal artery period (p = 0.016). No statistical differences were found in regard to race, diabetes status, glaucoma family history, and smoking., Discussion: Ophthalmic artery and central retinal artery computer-aided analysis of velocity waveforms could identify novel waveform parameters capable of differentiating among different demographics and disease severity of open-angle glaucoma patients.

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: Fecal calprotectin is a valuable non-invasive marker for intestinal inflammation and contributes to the selection of patients with suspected inflammatory bowel disease (IBD) for endoscopy. The aim of this study was to evaluate the performance of three automated immunoassays for fecal calprotectin (FC), fecal lactoferrin (FL) and fecal alpha-1-antitrypsin (A1AT) for diagnosis and follow-up of IBD, to investigate if automated analysis of this biomarker profile may further improve the diagnostic process, and to compare them to manual ELISA tests from different manufacturers., Methods: Stool samples from 72 patients with Crohn's disease (42), ulcerative colitis (17), irritable bowel syndrome (5), other gastrointestinal inflammation (8), and 72 healthy controls were analyzed for FC, FL, and A1AT on the automated Alegria® system (ORGENTEC Diagnostika, Germany). The results were verified by commercially available manual ELISA tests and discrepancies were further analyzed by immunoblotting. The fecal test results were correlated with the patients' endoscopic findings and with disease activity., Results: The automated assays FC and FL for Alegria® detected endoscopically active intestinal inflammation with a sensitivity and specificity of 74% and 87% (FC) and 62% and 87% (FL), respectively, and efficiently discriminated IBD from non-IBD samples in the patient cohort. Healthy controls tested negative in all assays. The results of the automated biomarker assays significantly correlated to those of the manual ELISAs. Alegria® results for FC were confirmed by immunoblotting in 7 discrepant samples. Levels of A1AT out of the normal range were detectable in a substantial number of IBD and irritable bowel syndrome (IBS) samples: 50% Crohn's disease, 35% ulcerative colitis, and 60% IBS, reflecting the disease-related changes of intestinal permeability in these patients. In IBD patients, elevated levels of A1AT correlated with relapsing disease., Conclusions: Measurement of FC concentrations with Alegria® is a convenient, promising, and useful tool for improving laboratory diagnostic accuracy and accelerating the diagnostic process and helps to identify those patients in whom endoscopy may be avoided. Automated analysis of a comprehensive profile of fecal biomarkers with Alegria®, including A1AT, provides further substantial benefit for laboratory diagnostics of IBD by improving stratification of patients for treatment and care.

To reveal the clinical significance of criteria and non-criteria antiphospholipid antibodies detected by line immunoassay in comparison with ELISA, systemic lupus erythematosus patients with and without thrombotic events were investigated. Thus, 107 systemic lupus erythematosus patients (48% with deep vein thrombosis or/and arterial thrombosis) and 120 healthy donors were enrolled. Serum antiphospholipid antibodies were detected by ELISA (Orgentec Diagnostika, Germany) and line immunoassay (GA Generic Assays, Germany). Lupus anticoagulant and IgG to cardiolipin and β2GPI but not IgM as well as triple positivity by ELISA and line immunoassay were linked with thrombosis in systemic lupus erythematosus. IgG to phosphatidylinositol and phosphatidylserine by line immunoassay showed significantly higher levels in systemic lupus erythematosus with deep vein thrombosis/arterial thrombosis than without and were independent risk factors for deep vein thrombosis (odds ratio 3.9, 95% confidence interval 1.1, 13.2) and arterial thrombosis (odds ratio 5.1, 95% confidence interval 1.3, 19.8) as well as thrombosis (odds ratio 3.6, 95% confidence interval 1.1, 11.3) and recurrence thereof (odds ratio 6.9, 95% confidence interval 2.1, 22.6), respectively. The occurrence of >4 IgG antiphospholipid antibodies by line immunoassay was an independent risk factor for thrombosis (odds ratio 10.9, 95% confidence interval 1.2, 101.5), arterial thrombosis (odds ratio 14.6, 95% confidence interval 2.5, 86.3), deep vein thrombosis (odds ratio 5.8, 95% confidence interval 1.0, 32.4) and recurrence of thrombosis (odds ratio 35.9, 95% confidence interval 3.8, 342.8). Line immunoassay is a promising multiplex test for the simultaneous detection of criteria and non-criteria antiphospholipid antibodies. Profiling of antiphospholipid antibodies by line immunoassay can differentiate systemic lupus erythematosus patients with thrombosis from systemic lupus erythematosus patients without and assess the risk for thrombosis and recurrence thereof.

Objective: To analyze the usage and timeliness of aquaporin-4 antibodies (AQP4-IgG) serology test in the diagnostics of neuromyelitis optica spectrum disorders (NMOSD) in routine clinical practice., Material and Methods: 27 patients with NMOSD were included in the study. All patients had a positive serum test for AQP4-IgG. A retrospective study of neurological manisfestations of attacks, timing and results of serology for AQP4-IgG was performed. The results were analyzed taking into account two types of attacks identified: a) HS (with highly specific manifestations for NMOSD), which are considered as indications for conducting the AQP4-IgG test and b) NS (with non-specific manifestations for NMOSD)., Results and Conclusion: A comparison of the time from HS attack to the AQP4-IgG test administration (T1, years), from HS attack to NMOSD diagnosis (T2, years) was undertaken as well as the number of attacks during these periods (N1, N2) were counted in three groups of patients. Group 1 - with the first HS attack before or in 2008 ( n =6), group 2 - from 2009 to 2013 ( n =12), group 3 - from 2014 to 2018 ( n =9) accordingly. A statistically significant decrease in T1, T2, N1, N2 was found in successive time intervals of 5 years ( p <0.05). In 8 of 27 (28.6%) patients the first attack of NMOSD was presented with non-specific symptoms (NS attack). In 7 patients (77.8%) of 9 misdiagnosed as multiple sclerosis (MS) an increase in attack frequency was found while on disease modifying therapies (DMTs) and increase in attack severity was found in 8 (88.9%). In all 9 cases the diagnosis was revised to NMOSD after AQP4-IgG test was performed with positive result. The time interval from disease course worsening while on DMTs until the test was 7 [4; 37] months, and the number of relapses - 2 [0; 3]. In 4 of 27 patients with suspected NMOSD, the repeated AQP4-IgG test only was positive for increased antibodies titer. The time interval between first test negative and retest administered was 20 [6.1; 47.8] months. In 3 of 4 patients (75%) one or more attacks occurred during this time period. In 4 patients the presence of AQP4-IgG in the first analysis was not followed by the diagnosis of NMOSD. In recent years, apropos AQP4-IgG test administration improved, but the problem remains with the timeliness for retest with first result negative. It is advisable to expand the indications for its use. The timeliness for serum AQP4-IgG retest in cases of unexplained deterioration in the course of proposed MS on DMTs and the lack of awareness of the test diagnostic value are still relevant.

Relapsing Evans syndrome (ES) and systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS) is very rare association. Coexistence of these syndromes is potentially fatal and require high-dose combined immunosuppressive therapy. We describe a case of successful use of Bortezomib and plasma exchange in a patient with ES and APS refractory to standard therapy. Thirty-two-year-old male who presented episodes of relapsing hemolytic anemia, pancytopenia and multiple thrombosis with positive direct and indirect antiglobulin test result, lupus anticoagulant and medium titer of anti-beta-2-glycoprotein 1 and anti-cardiolipin antibodies was diagnosed with ES and SLE with secondary APS. High-dose therapy by steroids and Cyclosporin A were started with temporary improvement. There was also no stable improvement with Rituximab and Cyclophosphamide. Bortezomib in combination with cyclosporine A and plasma exchange was introduced. He had stable improvement in hematological parameters with no evidence of relapse of hemolytic crisis or thrombosis during a follow-up for 1 year., (Copyright © 2018. Published by Elsevier Inc.)

Recent studies showed that B cells play a major role in the pathogenesis of neurodegeneration in multiple sclerosis (MS). In this study, we aimed to determine the possible link between immunoglobulin free light chains (FLC) and brain atrophy in patients with MS. Ninety-two patients (32 males and 60 females) with MS were included. Kappa and lambda FLC concentrations in serum and cerebrospinal fluid (CSF) samples of MS patients were measured using ELISA assay. FLC quotients (Q-k and Q-λ, respectively) were calculated. In a cross-sectional group (n = 92), the MRI data were acquired within 6 months from the date of the lumbar puncture. Twenty patients from this cohort performed a follow-up MRI after 1 year of observation. Brain volumes were calculated with SIENAX and the brain atrophy (percentage brain volume change (PBVC)) was assessed with SIENA. Spearman's test was performed to assess correlations. We have shown statistically significant correlation of Expanded Disability Status Scale (EDSS) level with normalized brain volume (NBV, r = - 0.2721, p = 0.0062), white matter volume (WMV, r = - 0.2425, p = 0.015), and gray matter volume (GMV, r = - 0.216, p = 0.0309). Multiple Sclerosis Severity Score (MSSS) score correlated with NBV (r = - 0.2521, p = 0.0352) and WMV (r = - 0.315, p = 0.0079). Neither EDSS, nor MSSS scores correlated with the age of patients and relapse rate during the first year and 5 years. In our study, we found statistically significant correlations of k-FLC in the CSF with NBV (r = - 0.311, p = 0.003) and with GMV (r = - 0.213, p = 0.0423). Q-k correlated only with NBV (r = - 0.340, p = 0.006) and Q-λ were negatively correlated with WMV (r = - 0.366, p = 0.003). We did not find correlations of k-FLC in CSF, λ-FLC in CSF, Q-k, and Q-λ with duration of MS course, EDSS, MSSS, number of relapses during the first year, and during the first 5 years of disease. Additionally, we subdivided the study population in accordance with level of k-FLC CSF, Q-k, and Q-λ on the 25th and 75th percentile subgroups (25-k-FLC CSF /75-k-FLC CSF ; 25-λ-FLC CSF /75-λ-FLC CSF ; 25-Q-k/75-Q-k; 25-Q-λ/75-Q-λ). We found statistically significant difference of NBV and GMV between 25-k-FLC CSF and 75-k-FLC CSF subgroups (p = 0.0047, p = 0.0297 respectively), NBV between 25-Q-k and 75-Q-k subgroups (p = 0.038), and NBV and WMV between 25-Q-λ and 75-Q-λ subgroups (p = 0.0446, p = 0.0026 respectively). PBVC in the prospective group showed negative correlation with kappa FLC in the CSF (r = - 0.4853, p = 0.0301) and Q-k (r = - 0.6132, p = 0.0224), but not with other clinical, epidemiological data. In this study, we showed a strong negative correlation of k-FLC, Q-k, and Q-λ with brain atrophy in MS patients. Additionally, patients with high concentration of FLC had lower brain volumes. We did not find correlations of FLC with the relapse rate, age of patients, and MS time course. In the prospective group, the rate of atrophy was correlated with k-FLC and Q-k. We suggest that level of intrathecal production of FLC can be a good prognostic biomarker for MS.

Vimentin is a protein of intermediate filament family, which is expressed in all mesenchymal cells. Vimentin plays a key role in the physiology of the cell, cellular interactions and the functioning of the immune system. Post-translationally modified and native forms of vimentin are involved in the pathogenesis of inflammation and many autoimmune diseases: rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, antiphospholipid syndrome, Crohn's disease, ankylosing spondyloarthritis and idiopathic pulmonary fibrosis. Modifications of the protein lead to the formation of antigenic epitopes and, as a result, to the synthesis of antibodies. Citrullinated, carbamylated and acetylated forms of vimentin participate in the pathogenesis of RA, and antibodies against them serve as diagnostic and prognostic markers of the disease. Epitopes of native vimentin are antigenic in the group of HLA-DRB1*0301 positive patients with sarcoidosis. In addition, vimentin takes part in pathogenesis of tubulointerstitial inflammation and glomerulonephritis in lupus. In antiphospholipid syndrome interactions of vimentin and cardiolipin on the surface of apoptotic cells lead to the formation of an immunogenic complex. Antibodies against vimentin/cardiolipin complex are involved in the mechanism of thrombogenesis and serve to identify patients seronegative for antibodies to cardiolipin and ß2glycoprotein-I with the clinical features. Post-translationally modified form of the protein is citrullinated and MMP-degraded vimentin, which was found in serum of patients with Crohn's disease and ankylosing spondyloarthritis., (Copyright © 2018. Published by Elsevier B.V.)

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

The secondary hemophagocytic syndrome is a life-threatening condition characterized by non-specifc manifestations: systemic inflammatory reaction, cytopenia, liver affection, high content of ferritin in blood serum. One of manifestations of secondary hemophagocytic syndrome is decreasing of level of glycated ferritin in blood serum expressed in percentage of total level. The detection of glycated ferritin can be applied for a differentiated diagnosis with cli9nically similar conditions, including septic process. The purpose of study was to determine clinical value of easurement of glycated ferritin for diagnostic and differentiated diagnostic of secondary hemophagocytic syndrome. The analysis was applied to samples of blood serum and clinical data of patients with diagnoses of secondary hemophagocytic syndrome (n=40), severe sepsis (n=24), cytolitic syndrome (n=36) and healthy donors (n=40). The total content of ferritin is established using rbidimetric technique ("BioSystems", Spain). The glycated ferritin was calculated. To determine level of of glycated ferritin the glycated fraction of ferritin was precipitated using concanavalin A, polymerized with sepharose 4B ("GE Healthcare", USA). The normal values of glycated ferritin made up to 78.3%-87.1%. Under secondary hemophagocytic syndrome decreasing of content of glycated ferritin made up to 25.0 ± 18.7% and was signifcantly lower than under sepsis (47.0 ±17.7%, p<0.001) and cytolytic syndrome(63.5% ±18.7%, p<0.001). According the results of ROC-analysis, the area under curve was maximal as compared with other markers of secondary hemophagocytic syndrome, including total ferritin, triglycerides, fbrinogen. At decreasing of level of glycated ferritin lower than 30.4% the applied technique provides clinical sensitivity 69%, specifcity 94.3%, accuracy 86.9% in applying differentiating diagnosis of secondary hemophagocytic syndrome. At calculation of absolute content of non-glycated ferritin it was discovered that its values correlate with concentration of triglycerides, international normalized ratio, aspartataminotransferase, alaninaminotransferase and total bilirubin in patients with secondary hemophagocytic syndrome (p<0.05). Therefore, decreasing of level of glycated ferritin permits to diagnose secondary hemophagocytic syndrome with higher accuracy., Competing Interests: The authors declare no conflict of interest.

The modern diagnostic approaches permit to diagnose axial spondylarthrosis (axSpA) at roentgenologic stage corresponding to ankylosing spondylitis (AS). While early diagnostic of non-roentgenologic axSpA (nr-axSpA) is still complicated. This situation conditions a need in searching new laboratory biomarkers for early diagnostic of spondylarthrosis, including auto-antibodies to antigen CD74 described recently. The purpose of study is to evaluate clinical diagnostic significance of auto-antibodies to antigen CD74 in case of axSpA. The technique of quantitative enzyme-linked immunosorbent assay was applied to measure content of auto-antibodies IgA to CD74 in samples of serum from 140 patients with axSpA: 68 with AS, 46 with nr-axSpA, 26 with psoriatic arthritis (PA) and 37 healthy representatives of control group with signs of axSpA totally clinically excluded. The average values of concentration of auto-antibodies IgA to CD74 in patients with axSpA and nr-axSpA made up to 3,5 ± 3,0 and 3,8 ± 2,9 U/ml correspondingly that reliably and significantly differed from patients with PA and healthy individuals - 2,1 ± 1,4 and 1,3 ± 1,4 U/ml correspondingly (p < 0,05). At threshold value of content of auto-antibodies IgA to CD74 higher than 2.0 U/ml in case of axSpA diagnostic sensitivity made up to 64.4%, specificity - 89.2%, risk factor of positive result - 5.9 whereas in patients with nr-axSpA at concentration 1.7 U/ml - 73,1%, 84% and 4,5 correspondingly. The auto-antibodies IgA to antigen CD74 are associated withaxSpA but not with PA that permits to use the given marker for diagnostic of axial spondylarthrosis and also in case of differential diagnostic between axSpA and PA., Competing Interests: The authors declare no conflict of interest.

Large number of studies was published about predictive value of cytokines for graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Recently, there has been a growing interest in GVHD prophylaxis with post-transplant cyclophosphamide (PTCy). Clinical data on the dynamics of proinflammatory cytokines with this prophylaxis is lacking. In this study, we have measured the levels of IL-17, IL-6, IL-8, IFN-γ and TNF-α in plasma on days -7, 0, +7, +14 and after engraftment in 20 patients with acute GVHD and 40 matched control patients with PTCy-based prophylaxis. Low levels of IL-8 (p=0.04) on day +7 and IFN-γ (p=0.03) after engraftment were associated with grade II-IV acute GVHD. The same pattern was observed for severe acute GVHD. Low IFN-γ after engraftment was also associated with increased non-relapse mortality (p=0.014). No impact of cytokine levels on overall survival and relapse incidence was observed (p>0.05). In conclusion, the dynamics of IL-8 and IFN-γ in GVHD patients after PTCy was different from previously reported after conventional prophylaxis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR) sequence. Expanded Disability Status Scale (EDSS) score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54) of patients. LMCE-positive patients had longer disease duration ( p = 0,0098) and higher EDSS score ( p = 0,039), but not a higher relapse rate ( p = 0,091). No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected ( p = 0,3842). Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume ( p = 0.043, F = 2.529), the total grey matter volume ( p = 0.043, F = 2.54), and total ventricular volume ( p = 0.039, F = 2.605). Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

The laboratory diagnostic of anti-phospholipid syndrome consists in detection of anti-phospholipid antibodies using technique of enzyme-linked immunosorbent assay namely in detection of anti-cardiolipin antibodies and antibodies to β2-glycoprotein. In spite of the fact that serological diagnostic plays a key role in diagnosing anti-phospholipid syndrome application of laboratory tests s complicated by their insufficient standardization. The new approach to detection of anti-phospholipid antibodies became application of immune blotting on the basis of polyvinylidenfluoride membrane. As compared with enzyme-linked immunosorbent assay, the advantage of the mentioned technique is in using hydrophobic solid phase for sorption of antigens. The porous structure of polyvinylidenfluoride membrane orientates hydrophilic areas of phospholipids and by that ensures their more dense distribution imitating bi-lipid layer of membranes of living organism. To specify and compare value of different techniques the comparison was implemented concerning the results of measurement of anti-phospholipid antibodies in enzyme-linked immunosorbent assay test-systems of various manufacturers and reagents kits for immune blotting. The collection was assembled including bio-materials from 47 patients with non-cardioembolic ischemic strokes, 20 patients with recurrent thrombosis of deep veins of lower extremities and 50 patients with obstetrics pathology and also 30 healthy donors. In the given serums aKlaIgG, aKlaIgM, aβ2glycoprotein I were measured using enzyme-linked immunosorbent assay technique assisted by test-systems of Euroimmun and Orgentes Diagnostica and the samples with the highest titre using immune blotting technique with reagents manufactured by Medipan. On the basis of measurement of anti-phospholipid antibodies by various enzyme-linked immunosorbent assay test-systems the rate of aβ2glycoprotein I amounted to 31% in case of Euroimmun reagents kits for enzyme-linked immunosorbent assay, 78% in case of Orgentec Diagnistica test-systems for enzyme-linked immunosorbent assay, aKlaIgG - 2% and 30%, aKlaIgM - 31% and 54% correspondingly. The measurement of anti-phospholipid antibodies using immune blotting technique on Medipan test-systems in bio-samples with the highest titres detected aβ2glycoprotein I in all patients, aKlaIgG in 70% and aKlaIgM in 30% of patients. The convergence between three commercial reagents kits varies from 20% to 88%. The standardization of commercial test-systems still to be achieved. The new technique of immune blotting can be appliedjointly with classic techniques ofserological diagnostic of anti-phospholipid syndrome. The absence of algorithms of diagnostic and standardization of different test-systems for detection of anti-phospholipid antibodies prejudices reliability of serological diagnosis of anti-phospholipid syndrome and therefore existence of anti-phospholipid syndrome as a nosologic unit.

Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated. This study was aimed at standardization and validation of a reporter cell system for measuring anti-human IFN-β NAb titers, and evaluation data were obtained with samples from 33 patients with multiple sclerosis.

The human recombinant β-interferon is most frequently applied for treatment of remittent recurrent form of multiple sclerosis using pharmaceuticals. The clinical response to applied therapy is absent in some of patients that can be conditioned by development of antibodies too preparations. Depending on possibility of blocking binding of human recombinant β-interferon with its receptor, all antibodies are divided on binding and neutralizing ones. The purpose of study is to investigate analytical and clinical diagnostic parameters of tests using for detection of different types of antibodies synthesized against human recombinant β-interferon. The study sampling consisted of 33 patients with remittent recurrent form of multiple sclerosis receiving therapy with human recombinant β-interferon and also of 40 donors and 15 patients with multiple sclerosis without therapy with human recombinant β-interferon. The concentration of binding antibodies was measured by enzyme-linked immunosorbent assay. Also immune blotting assay was applied. The titer of neutralizing antibodies was determined using cell line HL-116 sensitive to human recombinant β-interferon. The binding and neutralizing antibodies were not detected in donors and patients without human recombinant β-interferon therapy. The prevalence of binding antibodies to human recombinant β-interferon amounted to 57.6% when analysis of samples using immune blotting assay was used and 60.6% when commercial testing system was applied. The statistical analysis of results demonstrated high convergence and correlation of values of concentrations of binding antibodies obtained using immune blotting assay and enzyme-linked immunosorbent assay (r=0.9159, p<0.0001). The clinically significant titers of neutralizing antibodies were detected in 21.21°% of patients. All patients with clinically significant titer of neutralizing antibodies were positive in relation to binding antibodies measured by immune blotting assay and enzyme-linked immunosorbent assay. The high correlation between values of titers of neutralizing antibodies and concentration of binding antibodies measured by immune blotting assay (r=0.7909, p=0.0055). The application in clinical practice of data concerning presence of binding and neutralizing antibodies to human recombinant β-interferon can input into optimization of therapy with expensive biologic preparations in patients with multiple sclerosis and other autoimmune diseases.

Objectives: Clinical trials of IV-rituximab have proved successful. It is unclear whether intrathecal (IT)-rituximab is more efficacious at lower doses. We examine its effects on B-cell biomarkers., Methods: MS patients received IT-rituximab at 3 time-points. CSF and serum samples were obtained at up to 5 time-points (days 0, 7, 14, 56 and 112). Serum and CSF BAFF and CXCL13, and CSF kappa and lambda free light chains (FLC) were measured. Flow cytometry was performed, examining effects on lymphocytes, CD3-19+ and CD3-20+ cells., Results: CSF BAFF fell following rituximab (p=0.0091 absolute values, p=0.0284 change from baseline) whilst serum BAFF increased across time-points 1-4 (p=0.0005 absolute values, p=0.0017 change from baseline). There were significant reductions in CD20+ and CD19+ cells in blood from baseline (p<0.0001) but not in CSF. CSF kappa FLC levels significantly increased (p=0.0480)., Conclusions: BAFF levels fall in CSF but increase in serum following IT-rituximab. Rituximab appears to act peripherally with dramatic decreases in peripheral CD20+ and CD19+ cells. It is likely that CSF B-cell counts were too low to enable differences to be seen. The rapid reduction in B-cells suggests rituximab has immediate effects. The profound depletion of B-cells, despite low doses of rituximab, underlines rituximab's efficacy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The content of free light chains of immunoglobulins kappa and lambda and also ratio of their concentrations in blood serum are important diagnostic and prognostic markers in case of monoclonal gammopathy. The technique FreelightTM based on nephelometric detection of free light chains using polyclonal antibodies is one of common modes of detection of free light chains. The actual study was carried out with purpose of validating of national test-system for detection of level of free light chains in blood serum using technique of enzyme-linked immunosorbent assay. The samples of blood serum were taken from 89 healthy donors and 165 patients with monoclonal gammopathy. To detect the level of free light chains enzyme-linked immunosorbent assay testsystem "Polygnost" was used based on application of monoclonal a ntibodies. The number of analytical characteristics of reagents set was determined including limit of detection and range of linearity. The limit of detection of free light chains using enzymelinked immunosorbent assay test-system was two times lower than claimed by manufacturer of nephelometric set "FreelightTM". Hence, analytical characteristics of enzyme-linked immunosorbent assay set make it possible to detect the level of free light chains within range of standard values. The reference limits were established concerning concentration of free light chains kappa (3.25-15.81 mkg/ml), free light chains lambda (3.23-28.05 mkg/ml) and their ratio (0.3-1.9) in blood serum that factually matched the recommended intervals for "FreelightTM" set. In patients with monoclonal gammopathy the level of free light chains was reliably higher (p<0.01) as compared with control group of healthy donors. In case of paraproteinemia reliable alteration (p<0.01) of ratio free light chains kappa/free light chains lambda was observed in comparison with control group. The results of actual study testify that national enzyme-linked immunosorbent assay set has good analytical and diagnostic characteristics and it can be used in laboratory practice., Competing Interests: The authors declare no conflict of interest.

Background and Objective: In this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS)., Methods: We compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients., Results: The levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056)., Conclusion: The concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.

The qualitative and quantitative deficiency of alpha-1-antitrypsin (A1AT) is an inherited factor of susceptibility to a number of conditions including chronic obstructive disease of lungs and primary emphysema and liver affection. The study was carried out to evaluate analysis of alpha-1-fraction (A1F) using zonal electrophoresis technique for detecting patients with alpha-1-antitrypsin insufficiency (A1ATI). The patients with decreased (group I) and normal (group II) A1F on proteinogram. The electrophoresis was applied using the system of capillary electrophoresis Capillaris-2 Flex Piercing (Sebia, France) and also system for electrophoresis in agarose gel SAS-1/SAS-2 (Helena Biosciences, Great Britain). The commercial kit Sentinel diagnostics (Italy) and biochemical analyzer A15 (Biosystems, Spain) were used for quantitative detecting of A1AT The study results demonstrated that decreasing of A1F on proteinogram correlated with lessening of concentration of A1ATI in blood serum and with presence of its pathological phenotype. The average values of concentration of A1AT in group I and group II made up to 1148 and 1738 mg/I correspondingly. The total rate of pathological phenotypes made up to 76% (19/25) in group I that reliably differed from indicators in group II--7.1% (2/28). Thereby, electrophoresis of proteins of blood serum can be sufficiently informative for primary selection of patients requiring examination for presence of A1ATI.

The laboratory biomarkers can effect on choice of tactics of treatment in patients with atherosclerotic stenosis ofcarotids and high risk of stroke. However, nowadays there is no established laboratory criteria of significant atherosclerotic affection of internal carotid. The purpose of study was to investigate informativeness of biomarkers of atherosclerosis in clinical molecuIar panel of expertise system of determining risk of stroke in patients with significant stenosis of carotid. The study included patients with 50-90% atherosclerotic stenosis of internal carotid in acute period of atherothrombotic stroke or transitory ischemic attack (group 1), patients with stable 50-90% atherosclerotic stenosis of inner carotid having no vascular events during 30 days before engaging into study (group II) and group of healthy volunteers without atherosclerosis of inner carotid. The examination of patients included anamnesis collection, evaluation of neurological status, analysis of serum level of biomarkers of atherosclerosis (lipoprotein-associatedphospholipase A2 (LP-PL A2), serum protein A associated with pregnancy (PA PP-A), lipoprotein (a) (LP(a)), asymmetric dimethylarginine (ADMA), C-reactive protein detected by highly sensitive technique (hsCRP) and lipid spectrum of blood) using enzyme-linked immunosorbent assay, duplex ultrasound scanning of brachiocephalic arteries. The stroke risk factors of other etiology were chosen as exclusion criteria except atherothrombotic one. The Mann-Whitney and Kruskal-Wallis tests were applied to establish group differences. The Data Mining techniques were applied to establish patterns of analyzing sample. Out of 356 examined patients, 30 patients of group 1, 51 patients of group II and 16 healthy volunteers were included in the study. All patients were comparable by gender and age (50-80 years). The serum level of hsCRP and ADMA in the group of patients of acutest period of ischemic stroke was significantly higher than in groups of patients with stable stenosis and healthy volunteers (p < 0.05). The comparison between three groups established no statistically significant differences in serum concentration of PAPP-A, LP-PL A2 and LP(a). The ADMA, hsCRP and PAPP-A can be recommended for including into clinical molecular panel for personalized diagnostic of causes of stroke along with clinical anamnestic data. The serum level of ADMA and hsCRP significantly increases in acute period of atherothrombotic stroke. The analysis of levels of ADMA, hsCR and PPAPP-A interpreted with regard to clinical anamnestic data can be proposed for enhancing quality of diagnostic of causes of stroke.

Background and Objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort., Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS., Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres., Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation., (© The Author(s), 2015.)

Knowledge of mechanisms of infection in vulnerable populations is needed in order to prepare for future outbreaks. Here, using a unique dataset collected during a 2009 outbreak of influenza A(H1N1)pdm09 in a university town, we evaluated mechanisms of infection and identified that an epidemiological model containing partial protection of susceptibles best describes H1N1 dynamics in a rural university environment. We found that the protected group was over 14 times less susceptible to H1N1 infection than unprotected susceptibles. Our estimates show that the basic reproductive rate, R 0, was 5·96 (95% confidence interval 5·83-6·61), and, importantly, R 0 could be decreased to below 1 and similar epidemics could be avoided by increasing the proportion of the initial protected group. Moreover, several weeks into the epidemic, this protected group generated more new infections than the unprotected susceptible group, and thus, such protected groups should be taken into account while studying influenza epidemics in similar settings.

Data are rare on influenza outbreaks spreading through a workplace, but such transmission dynamics would be useful for comparison with the spread of the infection in other settings. We collected and compared infection data from two settings, a workplace and a university campus, during the 2009 pandemic influenza A(H1N1)pdm09 outbreak in a geographically contained community. Trajectories of infection were markedly alike in both settings. This suggests that transmission behaviour was similar in individuals in the two environments, despite the condition that individuals can leave the workplace setting in order to avoid transmission.

The article presents results of observation of generation of thrombin in patients with ischemic heart disease in different terms after transcutaneous coronary intervention. The sampling included 37 patients with stable ischemic heart disease. The control group included 30 healthy individuals. To study system of hemostasis of this category of patients the test of generation of thrombin and its modification with added thrombomodulin were applied for evaluating anti-coagulant activity of system of protein C. The comparison of indicators of test of generation of thrombin in patients with ischemic heart disease before operation and in individuals of control group revealed no reliable differences (p > 0.05). The observation of patients with stable ischemic heart disease in various time-frame after mechanical re-vascularization of myocardium established significant increasing of generation of thrombin and decreasing of anticoagulant activity of system of protein C at 1-3 day after operation (p < 0.05). The positive correlation was established between endogenous thrombin potential and annexin 5, an early marker of dysfunction of endothelium in mentioned time-frame after operation (p = 0.0008; r = 0.57). The significant increasing of content of anti-inflammatory markers of C-reactive protein and fibrinogen was observed at 1-3 day after transcutaneous coronary intervention (p < 0.05). In that way, the study data give evidence to hyper-coagulation in patients with stable ischemic heart disease in early time-frame after operation despite normal values of activated partial thromboplastin time, prothrombin time, D-dimer and applied standard disaggregant therapy.

Background. Mitoxantrone (MTX) and Rituximab (RTX) are successfully used for treatment of multiple sclerosis (MS) and can be combined to increase efficacy. Objective. We used MTX, RTX, and methylprednisolone in a single combined regiment and observed patients prospectively. Methods. We present results of observational pilot study of combined therapy of RTX and MTX in 28 patients with active MS. Therapeutic protocol consisted of two infusions within 14 days. First infusion was 1000 mg methylprednisolone (MP) IV, 1000 mg RTX IV, and 20 mg MTX IV. On day 14, 1000 mg MP IV and 1000 mg RTX IV were given. Patients were followed prospectively from 12 to 48 months. Results and Conclusion. There were no relapses among all 28 patients during the observation period. B-cell depletion of CD19+ and CD19+/CD27+ memory B-cell subpopulation in both compartments was confirmed in all patients at 6 months. We found a more rapid reconstitution of B cells in the CSF than in the peripheral blood and longstanding depression of CD19+CD27+ memory B-cell. Conclusion. Effectiveness of combined regimen of RTX and MTX could be related to longstanding depletion of CD19+CD27+ memory B-cell subset.

The article deals with comparison of clinical diagnostic value of laboratory techniques of tuberculosis. The sample included 63 patients with tuberculosis of lungs. 49 persons of long-time contact with patients with tuberculosis and 28 healthy donors. The QuantiFERON-TB Gold In-Tube test was applied to total sampling. The content of neopterin and specific anti-tuberculosis antibodies in blood plasma was determined. According study data, the mentioned test is mostly informative for detection of tuberculosis contamination (sensitivity 64%, specificity 89%). However, the obvious shortcoming of this technique is the fact that it can't provide the differentiation between active and latent tuberculosis infection. As opposed to QuantiFERON-TB Gold In-Tube test, the detection of specific anti-tuberculosis antibodies (sensitivity 54%, specificity 94%) and neopterin (sensitivity 51%, specificity 92%) makes it possible to differentiate these two groups of patients.

The study was carried out to determine clinical and immunologic predictors of unfavorable variant of course of ulcer colitis. The sample included 89 patients (48 females--53.9% and 41 males--46.1%) with ulcer colitis established on the basis of clinical, endoscopic and morphologic data. The age of patients was 18-79 years and mean age--42.49 +/- 1.61 years. The patients were divided on two groups depending on clinical course of disease: group 1 with favorable course and group 2 with unfavorable course. The group 2 included patients with frequently relapsing form of disease, patients with hormone-depended/hormone-resistant form of disease and patients with severe exacerbation ua ulcer colitis at the moment of examination. The groups were compared by gender and age. All patients underwent medical history and complaints acquisition and total clinical examination. The clinical and biochemical analysis of blood was made too. The severity of disease was established using the calculation of Trulove- Witts indicator The anti-neutrophil cytoplasmic antibodies of classes IgG and IgA were analyzed using indirect immunofluorescence (Euroimmun AG, Germany). The diagnostic anti-neutrophil cytoplasmic antibodies titer was established in 58 out of 87 of examined patients (66.6%). The antineutrophil cytoplasmic antibodies of class IgG was revealed in 42 patients and anti-neutrophil cytoplasmic antibodies of class IgA in 27 patients. The combination of both classes of anti-neutrophil cytoplasmic antibodies was established in 11 examined patients. In the group of favorable course of disease the diagnostic titer of anti-neutrophil cytoplasmic antibodies was revealed in 20 patients (51%). At the same time, in the subgroups with frequently relapsing, hormone-depended/hormone-resistant and severe forms of disease these antibodies were revealed with rate of 76, 77 and 86.3% correspondingly. Hence, the anti-neutrophil cytoplasmic antibodies can be used both in diagnostic of ulcer colitis and in prognosis of course of disease.

We have analyzed clinical presentations, neuroimaging data, blood and cerebrospinal fluid diagnostic tests in isolated angiitis of the central nervous system on the basis of data of recent publications and 22 our own cases. Due to the insufficient diagnostic value of invasive methods including biopsy of leptomeningeal and intracerebral vessels, we considered practical approaches to the diagnosis of cerebral vasculitis and ways of its optimization. We suggested the stratification of clinical, neuroimaging and laboratory criteria for the evaluation of their sensitivity and specificity and for the development of diagnostic algorithms.

The infections very often complicate the course of autoimmune rheumatic diseases. In diagnostic of septic complications in rheumatic patients the new biomarkers of infections can have a decisive importance. The procalciotonine test is one of them. The issue was to evaluate the diagnostic informativity of this test. The sample included 93 patients. The examination was applied to 65 patients with rheumatic diseases. Among them, 13 patients had bacterial infections. The group consisted of 33 patients with rheumatoid arthritis, 11 patients with systemic lupus erythematous, 6 patients with systemic angiitis, and 15 patients with other rheumatic diseases. The comparative group included 27 patients of cardio-therapeutic profile and 8 of these patients had bacterial infections. The procalcitonine test was applied with quantitative electrochemiluminescent technique. In patients with rheumatoid arthritis the mean levels of procalciotonine test consisted 0.10 +/- 0.13 ng/ml; with systemic lupus erythematous--0.08 +/- 0.06 ng/ml; with systemic angiitis--0.22 +/- 0.2 ng/ml; with other rheumatic diseases--0.12 +/- 0.15 ng/ml; of cardio-therapeutic profile without infections--0.08 +/- 0.06 ng/vl/ With threshold of procalcitonine test higher than 0.5/ml the sensitivity to diagnostic of infections consisted of 58%, specificity--94% in the group with rheumatic diseases. The procalciotonine test in case of no infection process with values higher than 0.5 ng/ml was detected in three patients. The evaluation of dependence of sensitivity and specificity for procalciotonine test and C-reactive protein the area under curve of procalcitonine test was larger in patients with rheumatic diseases (0.85 against 0.79) and in patients of cardio-therapeutic profile (0.92 against 0.90). The quantitative procalcitonine test is the best technique to detect septic complications in rheumatic patients.

In the vadose zone, air-water interfaces play an important role in particle fate and transport, as particles can attach to the air-water interfaces by action of capillary forces. This attachment can either retard or enhance the movement of particles, depending on whether the air-water interfaces are stationary or mobile. Here we use three standard PTFE particles (sphere, circular cylinder, and tent) and seven natural mineral particles (basalt, granite, hematite, magnetite, mica, milky quartz, and clear quartz) to quantify the capillary forces between an air-water interface and the different particles. Capillary forces were determined experimentally using tensiometry, and theoretically assuming volume-equivalent spherical, ellipsoidal, and circular cylinder shapes. We experimentally distinguished between the maximum capillary force and the snap-off force when the air-water interface detaches from the particle. Theoretical and experimental values of capillary forces were of similar order of magnitude. The sphere gave the smallest theoretical capillary force, and the circular cylinder had the largest force due to pinning of the air-water interface. Pinning was less pronounced for natural particles when compared to the circular cylinder. Ellipsoids gave the best agreement with measured forces, suggesting that this shape can provide a reasonable estimation of capillary forces for many natural particles.

The evaluation of diagnostic significance of different immunological tests for intrathecal immunoglobulin production is summarized on the historical basis of investigation of patients with inflammatory, demyelinating and other neurological disorders. The assessment of cerebrospinal fluid lost its previous significance in the 2010 revision of diagnostic criteria for multiple sclerosis. Nowadays, it is used only for the diagnosis of primary progressive multiple sclerosis. Nevertheless, the requirements of the analysis of the cerebrospinal fluid are increasing due to subtle, subclinical and atypical cases of multiple sclerosis as well as undetermined demyelinating disorders. Intrathecal humoral immune response may be pathogenic in multiple sclerosis as suggest immunological data and effectiveness of anti-B cells treatment. Based on these tests, it is useful, to differentiate subgroups of patients and to evaluate different effects of treatment in perspective.

The connective tissue systemic diseases originate from pathologic process following with antinuclear antibodies emergence. To detect these antibodies a significant number of diagnostic tests and techniques has been applied. Besides that, there is no conventional algorithm of antinuclear antibodies diagnostic. To detect antinuclear antibodies a two-fold diagnostic algorithm was applied In the capacity of screening techniques the indirect immunofluorescence technique was applied to the cells of line Hep-2 (antinuclear factor) and detection of antibodies to extractable nuclear antigen. The second stage of diagnostic included the detection of content of more specific antinuclear antibodies using the Lineblott method and the double-helical DNA antibodies. The blood serum from 981 patients with suspected connective tissue systemic diseases, 115 patients with systemic lupus erythematous and 57 healthy individuals was analyzed. The levels of antinuclear factor, nuclear antigen antibodies and double-helical DNA antibodies were detected. The antinuclear factor was detected in 84% and 86% of cases, double-helical DNA antibodies in 55% and 39% of cases depending of reagents using in detecting these characteristics. Among healthy individuals, antinuclear factor was detected in 5% (1/20) of blood serum samples in titers less than 1:160. In the group of patients with suspected connective tissue systemic diseases, antinuclear factor was detected in 48% (474/981) of cases and extractable nuclear antigen in 20% (326/981) of cases. The Lineblott test was positive in 33% (326/981) of patients with suspected connective tissue systemic diseases. Among antinuclear factor positive patients nuclear antigen antibodies were detected in 36% (171/474) and the Lineblott test was positive in 63% (298/474) of cases. Among antinuclear factor negative patients but positive under anti-nuclear antigen identification, the Lineblott test was positive in 6% (28/507) of cases. The two-fold algorithm of nuclear antigen testing is an effective technique to be applied in the clinical diagnostic laboratory. The results of effectiveness of this algorithm demonstrated that this method can ensure 33% of cost savings of testing individuals with higher incidence of diseases.

The clinical signifcance of serodiagnostic assay of rheumatoid arthritis increased nowadays. This is a reason to include the citrullinated antigens' antibodies into the new criteria of diagnostics ACR/EULAR 2010. The approbation of national test system detecting the cyclic citrullinated peptide antibodies was implemented. The analysis was applied to 211 blood serum samples taken of 50 blood donors, 60 patients with rheumatoid arthritis, 66 patients with other rheumatoid diseases. In addition, 35 samples were concurrently analyzed with the comparative test system (CCP2 Euroimmun, Germany). The referential meanings of standard limits were established on the basis of results of study of samples taken from healthy blood donors. When the standard limit was less than 10 arbitrary units the sensitivity made up 75% and the specificity--87.9%. In the case of higher values of citrullinated antigens' antibodies which are more than 15 arbitrary units, the sensitivity made up 68% and the specificity--93.1%. The results of comparing with the comparative test system characterized by high convergence made up 94% (33 out of 35), but the comparative test system detected citrullinated antigens' antibodies in 2 samples. The positive qualitative results of both methods analysis of autoantibodies weakly correlated with one another (r = 0.14). The results testify that the parameters of national test system correspond to the publication data concerning the second generation methods of cyclic citrullinated peptide antibodies detection though yield to the best foreign analogues.

Based on the own observations, we have summarized the features of symptomatic epilepsy in multiple sclerosis and conducted a clinical analysis of the most diagnostically difficult cases of inflammatory and demyelinating diseases in which epilepsy was the major clinical syndrome. The cases of post-infectious acute disseminated encephalomyelitis, idiopathic cerebral angiitis, Rasmussen's encephalitis are reviewed. Peculiarities of MRI structural brain lesions in these patients are discussed. The use of additional laboratory studies, including a study of cerebrospinal fluid, is considered.

A 52-year-old male presented with progressive dyspnea, bilateral leg edema, and elevated central venous pressure due to a large right atrial myxoma that caused vascular obstruction and pulmonary emboli. The myxoma contained gastric heterotopia. Other unusual features of this atrial myxoma included its large size, right atrial location, and attachment to the right atrial wall. Although gastric heterotopia has been reported throughout the gastrointestinal tract, and occasionally in other organs, this is the first report of gastric heterotopia in the cardiovascular system. This report confirms and extends previous reports of glandular elements or enteric glands within atrial, or cardiac, myxomas. The clinical presentation of the currently reported patient is explained as follows: the elevated central venous pressure resulted from cardiovascular obstruction and the dyspnea from multiple pulmonary emboli due to the large atrial myxoma. In this case, the clinical presentation was not attributable to the gastric heterotopia. The association of gastric heterotopia with atrial myxoma may, however, be clinically important because of the propensity of gastric heterotopia in the gastrointestinal tract to produce complications. The reported association may provide clues to the histogenesis of these two entities.

The method for determination of compliment activity from 50% hemolysis of sensitized blood cells (CH5) was modified in accordance with the recommendations of the International Clinical Chemistry Association, which could reduce the consumption of reagents, enhance the accuracy and reproducibility of results. The activity of CH50 was calculated for each serum sample by regression analysis, by graphically reflecting the results and by assessing the quality of each performance. The sigma-deviation method was used to calculate the normal CH50 ranges (55-160 conventional units) whose values were in compliance with the international standards. A series of experiments were made to assess the reproducibility of results. To evaluate the diagnostic informative value, the authors analyzed serum samples from 119 persons: 49 apparently healthy individuals, 74 patients with allergic diseases that are generally unattended by hypocomplementemia (Group 1) and 76 with disease the risk of which is increased in the presence of complement system defect (Group 2). Group 1 patients were those who had bronchial asthma or utricaria; Group 2 patients were those who had systemic lupus erythematosus, scleroderma, rheumatoid arthritis, chronic glomerulonephritis, acute glomerulonephritis, chronic furunculosis, chronic tonsillitis, or necrotic vasculitis. In Group 1, the value of CH50 was similar to that in the group of donors (108.0 +/- 3.1 and 105.1 +/- 3.8, respectively; p = 0.565), but it significantly differed from its mean value (91.6 +/- 5.1) in Group 2 (p = 0.00724). The difference in CH50 was also significant in the group of donors and Group 2 (p = 0.0349).

We performed this study in order to analyze the mechanical properties of bare-metal Wallstent endoprostheses and of AneuRx stent-grafts and to compare their responses to hemodynamic forces. Mathematical modeling, numerical simulations, and experimental measurements were used to study the 2 structurally different types of endoprostheses. Our findings revealed that a single bare-metal Wallstent endoprosthesis is 10 times more flexible (elastic) than is the wall of the aneurysmal abdominal aorta. Graphs showing the changes in the diameter and length of the stent when exposed to a range of internal and external pressures were obtained. If the aorta is axially stiff and resists length change, a force as large as 1 kg can act in the axial direction on the aortic wall. If the stent is not firmly anchored, it will migrate. In contrast, a fabric-covered, fully supported, stent-graft such as the AneuRx is significantly less compliant than the aorta or the bare-metal stent. During each cardiac cycle, the stent frame tends to move due to its higher elasticity, while the fabric resists movement, which might break the sutures that join the fabric to the frame. Elevated local transmural pressure, detected along the prosthesis graft, can contribute to material fatigue.

Aim: To assess diagnostic informative value of specific autoantibodies (AAB)--antikeratin antibodies (AKA), antiperinuclear factor (APF) and antibodies to cyclic peptide containing citrullin (CCP) from the family of antifilaggrine autoantibodies (AFA)--in rheumatoid arthritis (RA)., Material and Methods: A total of 121 patients with RA and 45 patients with seronegative spondylarthropathies. Rheumatoid factor was detected with latex agglutination. AKA and APF were estimated with indirect immunofluorescence the substrate of which was series frozen sections of rat esophagus in the middle third of 4 mcm and cells of the epithelium of the internal surface of healthy donor's cheek. For detection of antibodies to cyclic peptide, the test DIASTAT Anti-CCP ELISA (Axis Shield, Great Britain) was made., Results: The RF was detected in 67.8% patients with RA; AKA, APF and antibodies to CCP--in 43.6, 52.9 and 68.0% patients, respectively. AKA were most specific for RA (100%) while the RF was least specific among the AAB studied (87%). Simultaneous use of RF and AFA allows AAB detection in 84% RA patients at early stages of the disease. AFA were detected in patients with high clinico-laboratory activity of the process, high indices of functional joint insufficiency. 95% of all cases of destructive arthritis were detected in patients with RF, AKA, APF and antibodies to CCP., Conclusion: For RA patients it is necessary to determine both RF and AFA. Detection of AFA allows early diagnosis of RA as well as to single out patients with more aggressive course of the disease and unfavourable prognosis.