Institute of Clinical Immunology SB RAMS

Russia

Institute of Clinical Immunology SB RAMS

Russia

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Lykov A.P.,Institute of Clinical and Experimental lymphology SB RAMS | Konenkov V.I.,Institute of Clinical and Experimental lymphology SB RAMS | Gaidul K.V.,Institute of Clinical Immunology SB RAMS | Poveshenko O.V.,Institute of Clinical and Experimental lymphology SB RAMS | And 3 more authors.
Russian Journal of Biopharmaceuticals | Year: 2013

A screening of therapeutic efficacy of mechanically modified to sorption in nanostructured particles of colloidal silica forms of antibiotics, in comparison with their officinal forms, based on the dynamics of growth of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro and in experimental models of sepsis induced by various strains of microorganisms in mice (CBA×C57Bl6) F1 has been performed. The expediency of using this modification of antibiotics to enhance their therapeutic efficacy in experimental sepsis has been demonstrated.


Orlova D.Y.,Academy of Sciences of the Czech Republic | Orlova D.Y.,Masaryk University | Borisov V.I.,Institute of Clinical Immunology SB RAMS | Kozhevnikov V.S.,Institute of Clinical Immunology SB RAMS | And 2 more authors.
Journal of Theoretical Biology | Year: 2011

Though flow cytometry provides the entire distribution of cellular fluorescence (i.e., "fluorescence profile"), only mean fluorescence data are usually considered in studies of ligand-receptor binding. In this study, we presented a method of the treatment of the temporal evolution of the whole fluorescence profile with a comprehensive statistical approach extended to the reversible binding case. The method was demonstrated in the study of the 1D3 IgM monoclonal antibodies binding to FcγRIIIb receptors (CD16b) on neutrophils. Kinetic experiments were carried out using a FACSCalibur (Becton Dickinson, USA) flow cytometer. For each of four donors, we obtained the distribution of the number of FcγRIIIb surface receptors for neutrophils and the rate constants per receptor: the association rate constant of (2.7±0.4)×10 7M -1min -1, and the dissociation rate constant of (1.3±0.4)×10 -1min -1. Based on the obtained values, the size of the receptor reaction site was estimated at approximately 1nm. It was found, that cell receptors distributions differed sufficiently between donors in mean and the skewness values, whereas the coefficient of variation (i.e., the ratio of the standard deviation to the mean) did not vary significantly. © 2011 Elsevier Ltd.


Alchi B.,Addenbrookes Hospital | Jayne D.,Addenbrookes Hospital | Labopin M.,ADWP EBMT | Kotova O.,Novosibirsk State Medical University | And 14 more authors.
Lupus | Year: 2013

Objectives: Patients with systemic lupus erythematosus (SLE) refractory to conventional immunosuppression suffer substantial morbidity and mortality due to active disease and treatment toxicity. Immunoablation followed by autologous stem cell transplantation (ASCT) is a novel therapeutic strategy that potentially offers new hope to these patients. Methods: This retrospective survey reviews the efficacy and safety of ASCT in 28 SLE patients from eight centres reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 2001 and 2008. Results: Median disease duration before ASCT was 52 (nine to 396) months, 25/28 SLE patients (89%) were female, age 29 (1648) years. At the time of ASCT, eight (one to 11) American College of Rheumatology (ACR) diagnostic criteria for SLE were present and 17 (60%) patients had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte-colony stimulating factor in 93% of patients, and ex vivo CD34 stem cell selection was performed in 36%. Conditioning regimens were employed with either low (n=10) or intermediate (18) intensities. With a median follow-up of 38 (one to 110) months after ASCT, the five-year overall survival was 81±8%, disease-free survival was 29±9%, relapse incidence (RI) was 56±11% and nonrelapse mortality was 15±7%. Graft manipulation by CD34+ selection was associated with a lower RI (p=0.001) on univariate analysis. There were five deaths within two years after ASCT: three caused by infection, one by secondary autoimmune disease and one by progressive SLE. Conclusions: Our data further support the concept of immunoablation and ASCT to re-induce long-term clinical and serologic remissions in refractory SLE patients even in the absence of maintenance therapy. This study also suggests a beneficial effect of ex vivo graft manipulation on prevention of relapses post-transplantation in SLE. Lupus (2013) 22, 245253.© The Author(s), 2012.


Sergeevicheva V.V.,Institute of Clinical Immunology SB RAMS | Shevela E.Y.,Institute of Clinical Immunology SB RAMS | Sizikova S.A.,Institute of Clinical Immunology SB RAMS | Kulagin A.D.,Novosibirsk State Medical University | And 6 more authors.
Cellular Therapy and Transplantation | Year: 2010

Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients'MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis. © The Authors.


PubMed | Institute of Clinical Immunology SB RAMS
Type: Journal Article | Journal: Cytokine | Year: 2014

Dendritic cell-based vaccines are considered as a new and promising immunotherapeutic approach for cancer treatment. However, the choice of optimal protocol of dendritic cell generation in vitro represents the major challenge. Here, we compared phenotype and functional characteristics of human monocyte-derived dendritic cells (DCs) generated in the presence of IL-4/GM-CSF (IL4-DCs) and IFN/GM-CSF (IFN-DCs). We showed that IFN-DCs displayed semi-mature phenotype and expressed higher level of CD123, TNF-related apoptosis-inducing ligand (TRAIL) and B7-H1 molecules in comparison with IL4-DCs. LPS-stimulated IFN-DCs were characterized by greater production of Th1/pro-inflammatory (IFN-, IL-2, IL-1, TNF-, IL-17), h2/anti-inflammatory cytokines (IL-10, IL-5), hematopoietic growth factors (G-CSF) and chemokines (MCP-1). These data indicated more pronounced ability of IFN-DCs to induce cellular immune response as well as humoral immune response compared to IL4-DCs. LPS-stimulated IFN-DCs possessed higher direct cytotoxic activity against TRAIL-sensitive tumor cell line Jurkat and similar cytotoxicity against TRAIL-resistant tumor HEp-2 cells. Besides, IFN-DCs and IL4-DCs equally induced apoptosis of activated CD4(+) and CD8(+) T cells. These results suggest that IFN-DCs can be used as potent cell-based curative therapies for individuals with cancer.


Leplina O.Y.,Institute of Clinical Immunology SB RAMS | Tyrinova T.V.,Institute of Clinical Immunology SB RAMS | Tikhonova M.A.,Institute of Clinical Immunology SB RAMS | Ostanin A.A.,Institute of Clinical Immunology SB RAMS | Chernykh E.R.,Institute of Clinical Immunology SB RAMS
Cytokine | Year: 2015

Dendritic cell-based vaccines are considered as a new and promising immunotherapeutic approach for cancer treatment. However, the choice of optimal protocol of dendritic cell generation in vitro represents the major challenge. Here, we compared phenotype and functional characteristics of human monocyte-derived dendritic cells (DCs) generated in the presence of IL-4/GM-CSF (IL4-DCs) and IFNα/GM-CSF (IFN-DCs). We showed that IFN-DCs displayed semi-mature phenotype and expressed higher level of CD123, TNF-related apoptosis-inducing ligand (TRAIL) and B7-H1 molecules in comparison with IL4-DCs. LPS-stimulated IFN-DCs were characterized by greater production of Th1/pro-inflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-17), T{cyrillic}h2/anti-inflammatory cytokines (IL-10, IL-5), hematopoietic growth factors (G-CSF) and chemokines (MCP-1). These data indicated more pronounced ability of IFN-DCs to induce cellular immune response as well as humoral immune response compared to IL4-DCs. LPS-stimulated IFN-DCs possessed higher direct cytotoxic activity against TRAIL-sensitive tumor cell line Jurkat and similar cytotoxicity against TRAIL-resistant tumor HEp-2 cells. Besides, IFN-DCs and IL4-DCs equally induced apoptosis of activated CD4+ and CD8+ T cells. These results suggest that IFN-DCs can be used as potent cell-based curative therapies for individuals with cancer. © 2014 Elsevier Ltd.

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