Immunization of experimental autoimmune encephalomyelitis (EAE)‐prone C57BL/6 mice with MOG 35‐55 (a model used to study aspects of human multiple sclerosis) is known to lead to the production of various abzymes. The production of catalytic IgGs that can efficiently hydrolyse myelin basic protein (MBP), MOG and DNA is associated with changes in the profile of differentiation and level of proliferation of mice bone marrow haematopoietic stem cells (HSCs). As MOG simulates the production of abzymes with high DNase activity, we compared the effects of DNA and MOG immunization on EAE‐prone mice. In contrast to MOG, immunization with DNA leads to a suppression of proteinuria, a decrease in the concentrations of antibodies to MOG and DNA and a reduction in abzyme production. Immunization with DNA only resulted in a significant increase in DNase activity over 40 days where it became 122‐fold higher than before immunization, and fivefold higher when comparing to the maximal activity obtained after MOG treatment. DNA and MOG immunization had different effects on the differentiation profiles of HSCs, lymphocyte proliferation, and the level of apoptosis in bone marrow and other organs of mice. The data indicate that for C57BL/6 mice, DNA may have antagonistic effects with respect to MOG immunization. The usually fast immune response following MOG injection in C57BL/6 mice is strongly delayed after immunization with DNA, which is probably due to a rearrangement of the immune system following the response to DNA.

Experimental autoimmune encephalomyelitis (EAE)‐prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA–histone and DNA‐methylated bovine serum albumin (met‐BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG35‐55 results in the acceleration of EAE development. Anti‐DNA antibodies are usually directed against DNA–histone complexes resulting from cell apoptosis. During the acute EAE phase (7‐20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone‐DNA results in a reduction of proteinuria, a significant increase in anti‐DNA, anti‐MBP and anti‐MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA–histone and DNA‐met‐BSA only stimulated the formation of anti‐DNA antibodies hydrolysing DNA with a long delay (15‐20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA‐met‐BSA and DNA–histone complexes may have opposing effects compared to MOG. DNA–histone stimulates the appearance of histone‐hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time‐points. We conclude that MOG, DNA–histone and DNA‐met‐BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE.

The expression of cytokine receptors has a crucial role in many cellular processes. Recent studies reported that changes of receptor expression could control the action of mediators on target cells. The initiation of different signaling pathways and, therefore, specific effects on cells, depends on certain components forming the cytokine-receptor complex. These mechanisms control the immune response and affect both the course of diseases (oncological, autoimmune, inflammatory) and the effectiveness of therapy. This review describes the potential of immune mediator receptors to regulate the efficiency of cytokine activity during pathologic processes and ensure the variability of their biological effects. Our aim was to investigate the spectrum of potential roles of changes in mediator receptor expression for main classes of pathologies. For all major types of immune mediators (cytokines, interleukins, chemokines, growth factors, and tumor necrosis factors), it has been shown that changes in their receptor expression are associated with impaired functioning of the organism in chronic diseases.

Background. Atrial fibrillation (AF) and heart failure (HF) are tightly interrelated. The concurrence of these pathologies can aggravate the pathological process. The geographic and ethnic characteristics of patients may significantly affect the efficacy of different types of therapy and patients’ compliance. The objective of this study was to analyze how the features of the course of the diseases and management of HF + AF influence the clinical outcomes. Methods. The data of 1,003 patients from the first Russian register of patients with chronic heart failure and atrial fibrillation (RIF-CHF) were analyzed. The endpoints included hospitalization due to HF worsening, mortality, thromboembolic events, and hemorrhage. Predictors of unfavorable outcomes were analyzed separately for patients with HF and preserved ejection fraction (AF + HFpEF), midrange ejection fraction (AF + HFmrEF), and reduced ejection fraction (AF + HFrEF). Prevalence of HF + AF and compliance with long-term treatment of this pathology during one year were evaluated for each patient. Results. The study involved 39% AF + HFpEF patients, 15% AF + HFmrEF patients, and 46% AF + HFrEF patients. AF + HFpEF patients were significantly older than patients in two other groups (40.6% of patients were older than ≥75 years vs. 24.8%, respectively, p<0.001) and had the lowest rate of prior myocardial infarctions (25.3% vs. 46.1%, p<0.001) and the lowest adherence to rational therapy of HF (27.4% vs. 47.1%, p<0.001). AF + HFmrEF patients had the highest percentage of cases of HF onset after AF (61.3% vs. 49.2% in other patient groups, p=0.021). Among patients with AF + HFrEF, there was the highest percentage of males (74.2% vs. 41% in other patient groups, p<0.001) and the highest percentage of ever-smokers (51.9% vs. 29.4% in other patient groups, p<0.001). A total of 57.2% of patients were rehospitalized for decompensation of chronic heart failure within one year; the risk was the highest for AF + HFmrEF patients (66%, p=0.017). Reduced ejection fraction was associated with the increased risk of cardiovascular mortality (15.5% vs. 5.4% in other patient groups, p<0.001) rather than ischemic stroke (2.4% vs. 3%, p=0.776). Patients with AF + HFpEF had lower risk to achieve the combination point (stroke + IM + CV death) as compared to patients with AF + HFmrEF and AF + HFrEF (12.7% vs. 22% and 25.5%, p<0.001). Regression logistic analysis revealed that factors such as demographic characteristics, disease severity, and administered treatment had different effects on the risk of unfavorable outcomes depending on ejection fraction group. The clinical features and symptoms were found to be significant risk factors of cardiovascular mortality in AF + HFmrEF, while therapy characteristics were not associated with it. Conclusions. Each group of patients with different ejection fractions is characterized by its own pattern of factors associated with the development of unfavorable outcomes. The demographic and clinical characteristics of patients with midrange ejection fraction demonstrate that these patients need to be studied as a separate cohort.

Application of the protocol-identified differences in the percentage of cells that expressed TNFRs, as well as the absolute number of receptors per cell, among different subpopulations of PBMCs, and between PBMCs cultured with and without LPS.