Papers by Alexey Maslyanskiy
Annals of the Russian academy of medical sciences
Myocarditis and pericarditis are common pathologies in the general population, which pose signifi... more Myocarditis and pericarditis are common pathologies in the general population, which pose significant challenges to practitioners for both diagnosis and treatment due to the unique characteristics of diagnosis verification and lack of clear understanding of the diseases pathogenesis. This publication discusses the primary mechanisms of inflammatory diseases development of the myocardium and pericardium based on innate and acquired immunity disorders, including data from our research confirming the autoimmune and autoinflammatory nature of these diseases. The paper presents the main clinical manifestations and laboratory markers that enable differential diagnosis between autoimmune and autoinflammatory heart diseases. Additionally, it provides an evidence-based approach to the effectiveness of various anti-inflammatory and immunosuppressive drugs in different types and stages of inflammatory diseases of the myocardium and pericardium.
Clinical and Experimental Rheumatology
Objective Adult-onset Still's disease (AOSD) is increasingly viewed as autoinflammatory disease a... more Objective Adult-onset Still's disease (AOSD) is increasingly viewed as autoinflammatory disease associated with the so-called inflammasomopathy. Proinflammatory cytokines, such as IL-18 and IL-1β, processed through the inflammasome machinery, play an important role in the pathogenesis of AOSD. AOSD is heterogenous, therefore there are two subtypes of the disease, systemic and articular, which probably imply different approaches for the treatment. Over 20% of patients with systemic AOSD have serositis. Recently, colchicine in combination with non-steroidal anti-inflammatory drugs (NSAIDs) has become the "gold standard" for recurrent pericarditis treatment. However, data on this combination therapy in AOSD are scarce. Methods In this retrospective case series study, we assessed the medical history of 20 patients with a systemic form of AOSD. All patients had pericarditis and received а combination of NSAIDs (in most cases ibuprofen 600-800 mg x3 daily) and colchicine (1 mg daily) for treatment. Results 13/20 (65%) of patients responded to this combination of anti-inflammatory drugs. Of note, not only pericarditis, but also other manifestations were improved such as arthritis, rash, hepatomegaly, acute phase reactants, and abnormal l iver tests. Conclusion The low cost, safety and wide availability of such therapy make this option relevant and determine the need for further study.
Multiple Sclerosis and Related Disorders, 2016
Clinical trials of IV-rituximab have proved successful. It is unclear whether intrathecal (IT)-ri... more 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. 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. 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). 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.
Clinical and experimental rheumatology
ABSTRACT -
Bulletin of experimental biology and medicine, 2014
We studied the expression of some CC chemokines and their receptors in the synovium of patients w... more We studied the expression of some CC chemokines and their receptors in the synovium of patients with rheumatoid arthritis, osteoarthrosis, and a history of joint injury. In patients with rheumatoid arthritis, the levels mRNA for some angiogenic and proinflammatory chemokines (CCL5/RANTES, CCL11/eotaxin, CCL24/eotaxin-2, and CCL26/eotaxin-3) and their receptors (CCR1, CCR2, CCR3, CCR4, and CCR5) was elevated. mRNA expression correlated with activity, stage, and serological status of rheumatoid arthritis. Obtained data confirm the importance of CC chemokines as mediators of angiogenesis and inflammation in the synovium in rheumatoid arthritis.
Aging, 2011
The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) is an important negative regulator ... more The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) is an important negative regulator of signal transduction through the T-cell receptors (TCR). Recently a single-nucleotide polymorphism (SNP) 1858 C/T within this gene was shown to be a risk factor for several autoimmune diseases, such as rheumatoid arthritis (RA), Graves' Disease (GD), systemic lupus erythematosus (SLE), Wegener's granulomatosis (WG) and type 1 diabetes mellitus (T1D). The aim of this study was to analyze a possible association between 1858 C/T SNP and a number of autoimmune diseases, including RA, GD and T1D in Russian population. Patients with T1D, GD, RA and healthy controls were genotyped for the 1858 C/T SNP in PTPN22 gene. We found a significant association between PTPN22 1858 C/T SNP and T1D and GD. 1858T/T genotype was observed more frequently in T1D and GD patients compared to control subjects. No such association was observed for RA. In concordance with a previous data establishing PTPN...
Journal of Immunology Research, 2014
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic targets in systemic au... more Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic targets in systemic autoimmune rheumatic diseases (SARD). Loss of tolerance to the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1 and B2 has been the interest of rheumatologists. A novel ELISA for the detection of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence thereof in 397 patients with SARD, including patients with rheumatoid arthritis (RA), spondyloarthropathy (SPA), juvenile chronic arthritis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren’s syndrome (SS), in comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%;P<0.001). In particular, anti-hnRNP B1 were found more frequently in the disease cohorts than in the controls and were present in 24/165 (14.5%) patients with RA, 6/58 (10.3%) SPA, 11/65 (16.9%) SSc, ...
Biomarkers Thursday, October 11, 2012, 15:30 - 17:00 The effects of intrathecal rituximab on biom... more Biomarkers Thursday, October 11, 2012, 15:30 - 17:00 The effects of intrathecal rituximab on biomarkers in MS J. Topping, E. Evdoshenko, R. Dobson, S. Lapin, A. Maslyanskiy, G. Giovannoni (London, GB; Saint-Petersburg, RU) Introduction: There is increasing evidence for the role of B cells in MS, and a clinical trial of IV Rituximab, an anti-CD20 monoclonal antibody, proved successful. It is unclear whether intrathecal Rituximab is more efficacious at lower doses. Here we examine the effects of intrathecal Rituximab on the B-cell biomarkers BAFF, FLC and CXCL13, and on CSF and peripheral B cell populations. Methods and Materials 9 MS patients (4 RRMS and 5 SPMS; EDSS 4-8) received intrathecal Rituximab at 3 time points: 5mg on D0, 10mg on D7 and 15mg on D14. CSF and serum samples were obtained from all patients immediately prior to Rituximab dosing at up to 5 time points (days 0, 7, 14, 56 and 112). Commercially available ELISAs were used to measure BAFF and CXCL13 in serum and CSF, ...
Background. Mitoxantrone (MTX) and Rituximab (RTX) are successfully used for treatment of multipl... more 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.
Journal of the American College of Cardiology
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Papers by Alexey Maslyanskiy