[Autoimmune hearing loss and a chance of its development in children: literature review and own observations]. / Autoimmunnaya tugoukhost' i veroyatnost' ee formirovaniya v detskom vozraste: obzor literatury i sobstvennye nablyudeniya.

Autoimmune sensorineural hearing loss (AiSNHL) is an uncommon auditory disorder characterized by rapidly progressive bilateral hearing loss and a positive clinical response to treatment with corticosteroids and cytostatics. The prevalence of the disease in the adult population is less than 1% among all cases of subacute and permanent sensorineural hearing loss (precise data are unknown), it is even rarer in children. AiSNHL can be primary (isolated, organ-specific) or secondary (manifestation of another systemic autoimmune disease). The pathogenesis of AiSNHL is based on the proliferation of autoaggressive T cells and the pathological production of autoantibodies to the protein structures of the inner ear, which leads to damage to various parts of the cochlea (possibly also to the retrocochlear parts of the auditory system), less frequently to the vestibular labyrinth. Pathologically, the disease is most often represented by cochlear vasculitis with degeneration of the vascular stria, damage to hair cells and spiral ganglion cells, and endolymphatic hydrops. In 50% of cases, the result of autoimmune inflammation may be fibrosis and/or ossification of the cochlea. The most characteristic symptoms of AiSNHL at any age are episodes of sudden progression of hearing loss, fluctuations of hearing thresholds, and bilateral, often asymmetric impairments. The article presents contemporary ideas of the clinical and audiological manifestations of AiSNHL, the possibilities of diagnosing and treating the disease, and highlights the current approaches to (re)habilitation. Along with literature data, two own clinical cases of an extremely rare pediatric AiSNHL are given.

[Detection of paraprotein in plasma cell tumors].

Paraprotein is a laboratory biomarker of plasma cell tumors and other lymphoproliferative diseases. Its determination is necessary for diagnosing, monitoring and assessment of therapy effectiveness. The lecture presents the main methods of qualitative and quantative analysis of monoclonal proteins: gel electrophoresis, capillary electrophoresis, immunofixation and nephelometry features, possibilities and limitations are reviewed. The main sources of errors and artifacts during these studies are considered. Also the difficulties in the diagnosis and interpretation of the results of serum and urine tests are highlighted.

[The effect of non-invasive brain stimulation on neuroplasticity in the early recovery period after ischemic stroke]. / Vliyanie neinvazivnoi stimulyatsii golovnogo mozga na neiroplastichnost' v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

The post-stroke cognitive impairment syndrome (PSCI) develops in 10-80% cases of ischemic stroke and leads to a significant patients' quality of life impairment. The standard program of cognitive rehabilitation includes nootropic agents therapy and neuro-cognitive training. The additional various methods of non-invasive brain stimulation (NIBS) application can improve the results of PSCI rehabilitation. PURPOSE OF THE STUDY: Studying the different variants of NIBS influence on synaptic neuroplasticity in the early recovery period after ischemic stroke. MATERIAL AND METHODS: The rehabilitation of 62 patients with PSCI syndrome after ischemic stroke outcomes were studied. The patients were assigned to 5 groups. Patients from the control group underwent standardized nootropic therapy and course sessions with a neuropsychologist. The rest of the patients were divided into 4 groups, in which, in addition to the basic program of cognitive rehabilitation, different options for the course use of NIBS were used: photochromotherapy (PCT) with narrow-band optical radiation (NOR) with a wavelength of 530 nm (green light); rhythmic transcranial magnetic stimulation (rTMS) with a low-intensity high-frequency running pulsed magnetic field; infrared radiation with a wavelength of 1-56 microns, modulated by terahertz frequencies (IRMT); bioacoustic correction (BAC). We analyzed the dynamics of changes in scores of MMSE scales, FAB, Roshchina. In order to assess the effect of NIBS on neuroplasticity, the concentrations of BDNF and antibodies to the NR2 fragment of the NMDA receptor were evaluated before and after the completion of the rehabilitation course. RESULTS: Concentration values of antibodies to the NR2 subunit of the NMDA receptor in all groups remained consistently above the norm (more than 2 ng/ml) throughout the entire course of rehabilitation. Differences between groups in the dynamics of BDNF concentration in the peripheral blood were revealed. There was a significant (p<0.05) decrease in its concentration by almost 2 times by the end of rehabilitation course in control group. In the rTMS and IRMT groups, a decrease in the BDNF concentration was also recorded in dynamics, which, however, did not reach a significant level. There was no decrease in BDNF levels in the BAC group. There was an increase of this level in the PCT group. CONCLUSION: The use of different types of NIBS in the program of cognitive rehabilitation of patients with PSCI syndrome contributes to an increase in the rehabilitation potential due to the activation of neurotrophin-mediated synaptic neuroplasticity. Green light PCT and BAC have the greatest effect on increasing neuroplasticity after ischemic stroke.

Dependence of blood biochemical parameters on various genotypes of the UGT1A1 gene associated with gilbert's syndrome.

Diagnosis of Gilbert's syndrome is based on the detection of homozygous carriage of an additional TA-repeat in the promoter of the UGT1A1 gene, leading to a decrease in the activity of the UGT enzyme. No large studies have been done in the Russian Federation on the prevalence of carriage of Gilbert's syndrome, as well as the biochemical and molecular profile of such patients. The aim of the study is to evaluate biochemical and molecular genetic parameters in patients with Gilbert's syndrome in Russia. The study included 124 healthy volunteers (group 1) and 5650 patients with suspected Gilbert's syndrome (group 2). The number of TA-repeats of the promoter region of the UGT1A1 gene was determined by the method of fragment analysis for all participants. The following biochemical parameters were analyzed for 299 patients from group 2: the level of bilirubin and its fractions, AST, ALT, cholesterol and LDL. In group 1 the prevalence of genotype (TA)6/(TA)6 was 39,52%, (TA)6/(TA)7 - 53,23%, (TA)7/(TA)7 - 7,26%, no rare forms were found. In group 2 the prevalence of genotype (TA)6/(TA)6 was 6,04%, (TA)6/(TA)7 - 20,05%, (TA)7/(TA)7 - 73,7%, rare alleles - 0,2%. Rare alleles included (TA)5/(TA)6, (TA)5/(TA)7, (TA)6/(TA)8 and (TA)7/(TA)8, as well as a new genotype not described in the literature previously - (TA)7/(TA)9. When assessing the level of total bilirubin and its fractions, a difference was revealed between the genotype of Gilbert's syndrome (TA)7/(TA)7 and the reference genotype (TA)6/(TA)6, and between genotypes (TA)7/(TA)7 and (TA)6/(TA)7. A significant increase in total bilirubin was demonstrated in carriers of a larger number of TA-repeats. There was no significant difference in the concentration of ALT, AST, cholesterol or LDL between different genotypes.The number of TA-repeats of the UGT1A1 gene affects the increase of total bilirubin and its indirect fraction, including the cases of rare allelic variants (TA≤5, TA≥8), but not the activity of ALT and AST and the lipid profile.

Acrodystrophic axonal polyneuropathy with celiac disease: a case report.

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

[Analysis of urinary stone composition by infrared spectroscopy in the population of the European part of Russia].

INTRODUCTION: Urolithiasis is one of the most common urological diseases, which affect at least 3% of the population. AIM: To study the epidemiology of urolithiasis in the European part of the Russian Federation and to determine the composition of urinary stones in order to understand the pathogenetic mechanisms of urinary stones formation. MATERIALS AND METHODS: Urinary stone were obtained from 2888 patients with urolithiasis and the composition of kidney stones was analyzed using the method of infrared spectroscopy. RESULTS: The predominance of oxalate stones was seen in kidney stones with mixed composition (83%) and the prevalence of uric acid stones (54%) was revealed in "pure" kidney stones. Urinary stones with a predominance of oxalates had significantly less impurities (12,4%) than stones with a predominance of uric acid, phosphates and carbonates with average amount of impurities more than 24%. Conslusion. The analysis of stone composition with a consideration of pathogenic factor showed that disorders of calcium metabolism in the population of the European part of the Russian Federation prevailed (88%).

[Acute disseminated encephalomyelitis]. / Ostryi rasseyannyi entsefalomielit.

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.

Validation of the infrared spectroscopy method for analysis of the composition of urine concretes.

The aim of this study was to validate the method for analyzing the composition of calculus using infrared (IR) spectroscopy by studying model mixtures of salts. Study was made with an ALPHA-P IR Fourier spectrometer with OPUS software (Bruker, Germany). The samples of pure chemical salts manufactured by Sigma-Aldrich USA were used to validate the method. Salt mixtures were prepared in ratios of 10/90, 50/50 and 90/10. To assess the effect of the fraction size on the calculus component results, were used calculi of patients with urolithiasis. For each mixture were used 10 repeated measurements. Analysis of the composition of model salts showed that in the study of pure cystine salt CV(%) was 0,79%, calcium carbonate - 0,92%, sodium urate - 0,97%, calcium oxalate monohydrate - 4,94%, magnesium ammonium phosphate - 5,59%. And the most common components were analyzed in the composition of complex mixtures, including 90%, 50% and 10% of the investigated component. Calcium oxalate monohydrate has CV(%) 5.70% in mixture 9 part of it to one part of impurities, in mixture 50/50 - 21.57% and in 10/90 - 5.70%. For uric acid in 90/10 - 2.20%, in 50/50 - 10.09%, in 10/90 - 31.94%. For calcium carbonate in 90/10 - 9.02%, in 50/50 - 11.98%, in 10/90 - 24.70%. The dispersion analysis showed that the weighed portions of salts with a particle diameter of more than 0.8 mm provide reproducibility with a CV - 11.48%, with a diameter of 0.2-0.8 mm - 5.35%, and finally less than 0.1 mm - 2.28%. The accuracy of the method is high, but the reproducibility of the IR-spectroscopy method is relatively low in the analysis of stones of mixed composition, due to the greater error in the determination of impurities. Laboratories should pay special attention to optimizing sample preparation to ensure particle fineness less than 0.1 mm.

[Actual issues of serum aquaporin-4 autoantibodies evaluation in the diagnostics of neuromyelitis optica spectrum disorders]. / Aktual'nye voprosy diagnostiki zabolevanii spektra optikoneiromielita pri opredelenii antitel k akvaporinu-4 v syvorotke krovi.

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.

Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults.

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.

[The role of fraction analysis of ferritin in diagnostic of secondary hemophagocyte 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.

[The clinical diagnostic significance of auto antibodies to CD74 at axial spondylarthritis.]

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.

Profiles of pro-inflammatory cytokines in allogenic stem cell transplantation with post-transplant cyclophosphamide.

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.

[Membranous nephropathy in a Russian population]. / Membranoznaia nefropatiia v rossiiskoi populiatsii.

AIM: To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy. MATERIAL AND METHODS: MN cases in 2009 to 2016 were retrospectively detected with a subsequent analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect immunofluorescence assay. Treatment outcomes, such as the time course of changes in proteinuria, nephrotic syndrome (NS), and the development of complete and partial remissions (CR and PR), were assessed. RESULTS: MN was detected in 201 cases; the secondary etiology of the disease was established in 24.9%. The prevalence of MN among morphologically confirmed glomerulopathies was 14%; that of PMN was 10.4%. The median period to diagnosis PMN was 8 (5; 19) months. 150 patients with PMN (66.7% were men; age was 50±15 years) were distributed according to the following morphological stages: Stages I (23.9%), II (48.5%), III (26.1%), and IV (1.5%). Elevated anti-PLA2R Ab levels were found in 51.6% of cases; NS in the presence of proteinuria was detected in 85.6% of patients. An estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 was seen in 25% of cases. Treatment outcomes were evaluated in 80 cases; the median follow-up period was 19 (8; 40) months. 68% of cases had CR (32%) or PR (36%) with a median follow-up of 26 (13; 44) months. Spontaneous CRs or PRs were observed in 7.5% of the patients. Multivariate analysis showed that the probability of CR or PR increased 3.2-fold in the use of cyclophosphamide and/or cyclosporine and decreased as eGFR dropped. CONCLUSION: In Russia, PMN is a common type of glomerulopathy, the specific features of which should include the low rates of spontaneous remissions and detection of anti-PLA2R Abs. For renal protection, the majority of patients with PMN require timely diagnosis and treatment; individualization of the choice of treatment and its enhanced efficiency call for further investigations.

[Diagnostic value of immunoglobulin free light chains at the debut of multiple sclerosis]. / Rol' opredeleniia svobodnykh legkikh tsepei immunoglobulinov v diagnostike debiuta rasseiannogo skleroza.

AIM: To evaluate the diagnostic value of determination of free immunoglobulin light chains (IgG) in the debut of multiple sclerosis (MS). MATERIAL AND METHODS: Data from 226 patients, including 111 patients with clinically isolated syndrome with conversion to multiple sclerosis within the first 2 years of the disease (group 1), 49 patients with clinically isolated syndrome who did not develop multiple sclerosis within the first 2 years of the disease (group 2), 20 patients with other inflammatory diseases of the central nervous system (group 3) were analyzed. The control group consisted of 46 patients with non-inflammatory diseases of the central nervous system. The clonality of immunoglobulins in the CSF, concentration of kappa and lambda free light chains and their ratio were studied. RESULTS: Concentrations of free light chains were significantly higher in the first group in comparison with group 2 and the control group, but didn't differ from group 3. In group 3, concentrations of free light chains were significantly higher compared to group 2 and controls. In oligoclonal-positive patients with clinically isolated syndrome (groups 1 and 2), concentrations of kappa and lambda free light chains were significantly higher than in oligoclonal-negative patients. The production of free light chains in patients from the first group was considerably higher than in group 2 regardless of the oligoclonal status. The concentration of kappa chains and quotient of kappa free light chains in the CSF had the best diagnostic characteristics. Their use, along with the evaluation of IgG clonality, reduced the risk of false-negative results by 50%. Regardless of other factors, elevated concentrations of kappa chains increase the likelihood of MS diagnosis by 9.718 times. CONCLUSION: The use of free light chains as a laboratory marker can increase the accuracy of MS diagnosis. These markers can help indirectly assess the risk of transformation of a clinically isolated syndrome into definite multiple sclerosis within the first 2 years of disease.

[The comparative analysis of immunologic techniques of detection of anti-phospholipid antibodies].

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 ß2-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, aß2glycoprotein 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 aß2glycoprotein 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 aß2glycoprotein 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.

[The association of intrathecal production of immunoglobulin free light chains and progression of multiple sclerosis]. / Sviaz' intratekal'noi produktsii svobodnykh legkikh tsepei immunoglobulinov s progressirovaniem rasseiannogo skleroza.

AIM: To assess an impact of immunoglobulin free light chains (FLC) on short-term and long-term prognosis of clinical and radiological activity and progression of disability in multiple sclerosis (MS). MATERIAL AND METHODS: A sample of 381 patients with definite MS was divided into 2 groups. In group 1, lumbar puncture was performed at the time of clinically isolated syndrome, and patients were prospectively followed up to 2 years (short-term prognosis group, n=97). In group 2, MS was diagnosed immediately after lumbar puncture, and retrospective analysis of the disease course with the duration not less than 5 years was performed (long-term prognosis group, n=284). The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) were used to assess patient's status. Concentrations of kappa and lambda FLC in the CSF (K-FLCCSF, L-FLCCSF) and serum (K-FLCSERUM, L-FLCSERUM) as well as quotients of concentrations (Q-K and Q-L) were determined. Patients were stratified into subgroups with high and low concentrations of K-FLC and L-FLC using cut-offs from our previous studies: K-FLCCSF=0.595 mcg/l and L-FLCCSF=0.127 mcg/l. RESULTS: In group 1, significant correlations were found only between EDSS score and concentrations of K-FLCCSF (r=0.377, p=0.00019) and Q-K (r=0.366, p=0.0012). FLC concentrations did not correlate with the number of relapses and new T2 lesions. The age and EDSS score at the disease onset didn't differ between patients with high and low K-FLC and L-FLC (K-FLCCSF: р=0.2658; L-FLCCSF: р=0.5502). A significant decrease of EDSS score after the disease onset was observed in all groups except for patients with high concentrations of K-FLCCSF (p=0.1844), so the EDSS score after 2 years was significantly higher in this subgroup of patients (p=0.0006). In group 2, significant correlations of K-FLC with EDSS score (r=0.181, p=0.002) and MSSS score (r=0.121, р=0.044) for long-term prognosis (median (IQR) = 8 (6-13) years) were found. No correlations of FLC concentrations with the number of relapses during the first 5 years were found. Survival analysis showed that high concentrations of K-FLCCSF were associated with the high risk of progression to EDSS 6 (HR=2.055, p=0.026) but not with EDSS 4 (HR=2.388, p=0.08). CONCLUSION: Concentrations of kappa FLC can help to define the prognosis of MS early at the disease course. Although low concentrations of FLC do not exclude a severe disease phenotype, patients with high K-FLCCSF concentrations are at greater risk for faster MS progression, probably, due to impaired reparation of neural tissue. Measurement of FLC concentrations can be used to determine a therapeutic tactics in patients with MS.

Immunogenicity of Human Interferon-Beta-Containing Pharmaceuticals.

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-ß)-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-ß activity also quantifying NAb level are applied because direct measurement of IFN-ß antiviral activity is complicated. This study was aimed at standardization and validation of a reporter cell system for measuring anti-human IFN-ß NAb titers, and evaluation data were obtained with samples from 33 patients with multiple sclerosis.

[Coexistence of pulmonary sarcoidosis and primary Sjögren's syndrome].

The paper describes a case of a rare coexistence of primary Sjögren's syndrome (PSS) and sarcoidosis in a 41-year-old female with histologically verified lung and locomotor system diseases and keratoconjunctivitis sicca. PSS was diagnosed based on the 2012 ACR classification criteria, in the framework of which serological, histological, and gland function tests and instrumental diagnostic methods were performed. The diagnosis of sarcoidosis was based on clinical, radiographic, and histological findings.

[Current concepts on intrathecal humoral immune response and diagnostic importance of oligoclonal immunoglobulins in multiple sclerosis]. / Sovremennye predstavleniya ob intratekal'nom gumoral'nom immunnom otvete i diagnosticheskoe znachenie vyyavleniya oligoklonal'nykh immunoglobulinov pri rasseyannom skleroze.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system of probable autoimmune origin. In this review of literature, the authors present a constantly broadening list of potential antigens, including myelin and non-myelin structures, that cause the autoimmune reaction. Determination of antibodies to any antigen has not sufficient specificity and sensitivity for the use in routine laboratory practice. Oligoclonal immunoglobulins determined with isoelectric focusing (IEF) technique are currently considered as the main immunological MS markers. The sensitivity and specificity of IEF are 90 and 86%, respectively. The authors have considered the additional markers such as oligoclonal IgM and MRZ-response.