Abstract. The review article considers different variants of measles vaccine that may be classified into two groups, i.e., vaccines that do not contain viable measles virus, and attenuated measles vaccines which could be employed in unusual manner.

The first group includes DNA-vaccines, recombinant vaccine strains encoding synthesis of measles hemagglutinin and fusion protein, as well as peptide vaccines containing molecular fragments of these proteins. The mentioned variants of vaccines were effective in animal experiments, but they have not been tested in humans. The second group includes live attenuated mucosal measles vaccins applied in combination with immunomodulator(s), as aerosol and intranasally. Efficiency of these vaccines was tested and confirmed by immunization of children and adults. Mucosal measles vaccine induces local production of IgA measles antibodies, along with induced synthesis of circulating IgM and IgG antibodies against measles. The latter experimental variant could be a live attenuated measles vaccine containing some immunity-modulating agent. Elaboration of these variant was based on the known data about transient immunosuppressive activity of measles vaccine. An appropriate experimental variant represents a mixture of attenuated measles vaccine and synthetic immunomodulating agent (MP-2 peptide) which protects T-lymphocytes from inhibitory effect of the measles virus. In present revue, some data are presented concerning the mechanisms of immunogenic activity and adverse effects of measles vaccines.

Abstract. Our understanding of the multiple physiological and pathological functions of B-cells continues to expand at a fascinating rate. As pathogenic elements in the development of autoimmune diseases, B-cells have become the focus of new therapeutics. Based on the published data, rituximab, a chimeric monoclonal antibody to CD20, when used in combination with other agents (i.e., cyclophosphamide or methotrexate), appears to be a reasonable treatment option for refractory RA. There are now numerous case reports and small openlabel series using rituximab in many autoimmune diseases, others then RA. While these data must be interpreted with caution, they suggest that rituximab may be a promising addition to the therapeutic armamentarium in these diseases. However, additional controlled trials need to be conducted to confirm clinical efficacy, further define optimal dosage, response rates, comparative long-term efficacy, and treatment algorithm for rituximab in these patients.

Abstract. Physiological and biochemical changes proceeding in muscles during physical loads exert systemic influence upon protein biosynthesis. This process is accelerated in presence of free amino acids, sufficient quantities of hormones, creatine, hydrogen ions. High proton concentrations in tissues and longitudinal physical loadings upon human organism suppress the protein biosynthesis, thus leading to decomposition of hormones, immunoglobulins and cell damage. These changes may explain the development of various immunodeficiencies in sportsmen.

Abstract. The role of different B-cell subpopulations in polyclonal B-cell activation induced by T-independent antigens type 2 (TI-2) was under studies. CD5+B/B-1 cells were isolated from the spleens of mice immunized with polyvinyl pirrolidone, or á(1→3) dextran. The numbers of antibody (Ab) and Ig-producers in CD5+B/B-1 splenocytes were determined by ELISPOT. The number of cells producing unspecific Ig was calculated as a difference between the numbers of Ig- and Ab-producers; the numbers of nonspecific Ig-producing splenocytes induced by TI-2 immunization were determined as differences between their contents in immunized and control animals. In experiments with CD5+ and CD5– splenocytic populations, the development of Ab-producers and increased numbers of cells producing unspecific Ig was dependent on the CD5+ B-cells. These data were confirmed in experiments with subpopulations of B-1 and B-2 lymphocytes obtained with Dynal separation kit. In spite of sufficient predominance of B-cells in B-2 fraction (91% vs ~13% in B-1 fraction), the numbers of Ab and TI-2-induced nonspecific Ig-producers were nearly similar for the both cell fractions. Taking into account relative contents of B-cells, the numbers of Aband unspecific Ig- producers in B-1 fraction were 6- to 7-fold higher than in B-2 fraction. Thus, dependence on the B-1 cells exists both for polyclonal immune reactions to polyvinylpirrolidone and dextran, and specific response. Simultaneous injection of two TI-2 antigens did not induce additive effects upon the numbers of unspecific Ig-producers in B-1 fraction, in spite of marked increase in amounts of these cells after separate immunization with either of these antigens. It is concluded that polyclonal activation of B-1 cells by TI-2 antigens is subject to restriction which may depend either on the size of B-cell pool available for activation, or on insufficiency of appropriate stimulating factors.

Abstract. Alpha-1-acid glycoprotein (orosomucoid) is a multifunctional acute phase reactant belonging to the family of lipocalines from plasma alpha-2 globulin fraction. In present study, we investigated dosedependent effects of orosomucoid upon secretion of IL-1â, IL-2, IL-3, IL-4 by mononuclear cells from venous blood of healthy volunteers. Mononuclear cells were separated by means of gradient centrifugation, followed by incubation for 24 hours with 250, 500, or 1000 mcg of orosomucoid per ml RPMI-1640 medium (resp., low, medium and high dose). The levels of cytokine production were assayed by ELISA technique. Orosomucoid-induced secretion of IL-1â and IL-4 was increased, whereas IL-3 secretion was inhibited. IL-2 production was suppressed at low doses of orosomucoid, and stimulated at medium and high doses. The effect of alpha-1-acid glycoprotein upon production of IL-2, IL-3 and IL-4 was dose-dependent. Hence, these data indicate that orosomucoid is capable of modifying IL-1â, IL-2, IL-3, and IL-4 secretion by blood mononuclear cells.

Abstract. The article is considering certain features of immunopathogenesis exhibited in persistent viral infections, taking into account modern data and recently introduced immunological techniques. It has been revealed that a long-term persistence of hepatitis B and C viruses, tick-borne encephalitis, and herpes simplex is accompanied by deficient functioning in the T-cell compartment of immune system, and by markedly altered production of immunoregulatory cytokines in peripheral blood mononuclear leukocytes, mainly characterized by Th2 predominance.

Abstract. The levels of autoantibodies to collagen type I, II, III, IV and V were studied in blood plasma of 130 patients (18-32 years old) with undifferentiated connective tissue dysplasia, using immunoenzyme analysis. A correlation was revealed between the levels of autoantibodies to various collagen types, and external and/or heart manifestations of connective tissue dysplasia. Increased levels of autoantibodies to collagen type I and II were shown in patients with chest deformation, scoliosis, pronounced joint hypermobility syndrome, multiple minor intracardial anomalies. Increased antibodies to type I collagen were associated with flat-footedness, whereas levels of antibodies to collagen type I, II, and V correlated with myxomatous degeneration of mitral valve prolapse. Increase in anticollagen antibody levels in cases of pronounced external and cardiac markers of connective tissue dysplasia suggests an impairment of autoimmune regulatory mechanisms of collagen metabolism.

Abstract. Presence of some antinuclear antibodies (ANA)is a typical feature of connective tissue disorders (CTD), such as systemic lupus erythematosus (SLE), Sjogren’s syndrome, rheumatoid arthritis (RA). The purpose of our work was to estimate the significance of laboratory tests commonly used in CTD.

We examines blood serum collected from 1312 patients with suspected connective tissue disorders, 105 patients with confirmed SLE, 163 patients with RA, 15 patient with Sjogren’s syndrome (SS), and 100 healthy volunteers. Blood serum was tested for antinuclear factor (ANF) using HEp-2 method, antibodies against extractable nuclear antigens (anti-ENA), line blot ANA, IgG antibodies against double-stranded DNA (anti-dsDNA IgG), IgG and IgM antibodies against cardiolipin (CL) and beta-2-glycoprotein 1 (B2GP1). The Crithidia luciliae immunofluorescence (CLIF) assay was also used to detect antibodies to native dsDNA.

ANF prevalence in the patients with suspected CTD was 23,4% (309/1318). Speckled pattern of ANF was detected in 100% (15/15) of patients with SS. Prevalence of ANF in patients with SLE and RA was 79% and 36%, correspondingly. ANF was revealed only in 3% of healthy volunteers and its titer did not exceed 1/80. Blood serum from 282 patients was tested for ANF and anti-ENA. Coincidence of ANF and antibodies against ENA were found in 12% of cases (34/282), and isolated anti-ENA – in 7% of cases (20/282). In this group (anti-ENA-positive/ANF negative), antibodies to SS-A antigen were detected in 64% of patients, using ANA lineblot, 36% of patients were negative. Blood sera from 614 patients were tested, in order to evaluate coincidence of ANF and anti-dsDNA. The antibodies were revealed in 45.9% of cases, whereas a combination of ANF and anti-dsDNA in diagnostic titers was found in 151 patient. Anti-dsDNA in absence of ANF were detected in 14.9% (42/282) of patients; in 6.7% of the samples (19/282), higher concentrations of antibodies were detected (> 50 IU/ml). In conclusion, ANF sensitivity was 63% vs 35%, specificity – 89% vs 95% in the groups of patients with dsDNA antibodies, resp., > 25IU/ml, and > 50 IU/ml. In the patients examined for anti-CL, ANF and anti-dsDNA, high concentration of anti-CL without detectable ANF and anti-dsDNA was found only in one case; in the rest of patients, high titers of anti-CL were associated with higher titers of ANF and anti-dsDNA, thus indicating high probability of rheumatic diseases (most likely, SLE) in these patients.

Informativity of the methods used for CTD diagnostics is increased, when several autoantibodies are detected concomitantly, thus allowing optimized immunological examination of the patients with rheumatic diseases.

Abstract. To study the value of antibodies to cirtullinated antigens in diagnosis and their significance in prediction of erosion formation of rheumatoid arthritis (RA), we examined serological status in 129 patients with early RA (ERA) and 55 cases of undifferentiated arthritis, lasting less than 12 months. Another group consisted of 39 patients with long-standing rheumatoid arthritis, in whom the disease persisted for > 2 years. Control group included 39 patients with osteoarthrosis and 29 patients with reactive arthritis. The titers of rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF) and antibodies to cyclic citrullinated peptide (anti-CCP) were studied during initial examination and 12 months later. Serial cryosections of rat esophagus and normal human buccal epithelial cells served as substrates for AKA and APF detection. AntiCCPs were revealed by means of DIASTAT technique (Axis Shield, UK).Upon initial observation of the patients with ERA, sensitivity and specificity of anti-CCP was, resp., 63.5% and 97,8%, thus exceeding both parameters for RF (48,8% и 86,7%). Sensitivity of AKA and APF for the same group was 17% and 24 %, with specificity of 97.7%. In RF-seronegative cases of early RA, anti-CCP were detected in 37% with ERA and 42% long-standing RA. In patients with non-differentiated arthritis who developed RA within one year, RF and anti-CCP were found in 12,2% and 45,5%. Following a one-year observation, a statistically significant increase was found in incidence of RF and anti-CCP in ERA patients.

Positivity for anti-citrulline antibodies (AKA, APF and anti-CCP) in ERA patients were associated with higher levels of CRP, increased HAQ, DAS4, Sharp scores, as compared to the patients who were seronegative. In ERA patients positive for anti-citrulline antibodies, higher frequencies of synovitis and erosive arthritis were detected by means of ultrasound and magnetic resonance imaging. In the patients with ERA, both RF- and anti-CCP seropositivity represent sufficient risk factors for erosive arthritis within a year after clinical manifestations.

Abstract. Endometriosis is a disease accompanied by development of heterotopic endometrial foci at the peritoneum, proliferation of endothelial cells, and inflammatory reaction. Aiming to specify the dynamics of inflammatory process in endometriosis of different severity, as well as significance of chemokines and cytokines in angiogenesis and inflammation, we determined concentrations of RANTES, IL-8, IP-10, MIG, MCP-1 chemokines, as well as IL-4, IL-6 and IL-10 cytokines in peritoneal fluid from patients by endometriosis. Forty women at reproductive age with an endometriosis have been observed. Among them, endometriosis grade I-II was registered in 20 cases, whereas grade III-IV has been confirmed in 20 women. Twenty-two women without evidence of endometriosis referred to diagnostic laparoscopy for pregnancy planning, comprised a control group. Diagnosis of endometriosis was based upon endoscopic findings and results of histological research. Severity grade of endometriosis was estimated according to R-AFS classification. Sampling of peritoneal fluid was carried out when performing surgical laparoscopies. Concentrations of chemokines and cytokines were determined by flow cytometry techniques, using BD Cytometric Bead Array test kits and FACStrack flow cytometer. The amounts of RANTES in peritoneal fluid were higher in grade I-II endometriosis, in comparison with grade III-IV endometriosis and control samples. Concentrations of IP-10, IL-8, МСР-1, MIG, IL-6, and IL-4 were higher than in control group and correlated with severity of the disease. IL-10 was not detectable in peritoneal fluid of the patients with endometriosis. These results suggest a significant role of the mentioned cytokines and chemokines that may promote invasion of endometrial cells, growth of heterotopic endometrioid locuses, development of vascular bed and induction of inflammatory processes, in development and progression of endometriosis.

Abstract. The aim of present study was to investigate the ratios of semen lymphocyte subpopulations in males with infertility. Twenty-six men (20 to 45 years old) suffering from different genital diseases (chronic prostatitis, idiopathic varicocoele, testicular atrophy) were enrolled into the study. Six healthy age-matched normozoospermic male volunteers with normal fertility comprised a control group. Lymphocyte phenotyping was performed by flow cytometric technique. The patients with pathospermia showed increased numbers of CD25+ lymphocytes (p < 0.05), and unchanged levels of CD95+ cells, thus leading to increased CD25+/CD95+ ratio. In the patients with normozoospermia, the value of this index was 0.94±0.18. Increase of this parameter to > 1.2, as well as its reduction to < 0.7 was associated with sterility. We suggest that suppressed apoptosis of activated lymphocytes in semen may be potentially dangerous to spermatogenesis, since both immune response and associated inflammatory reactions can cause nonspecific lesions of surrounding tissues, and induction of pathospermia.