REVIEWS
There is a genetic predisposition to psoriasis (PS) and psoriatic arthritis (PsA), in which some cytokine genes are involved. Identification of polymorphic variants of immune response genes (i.e.,cytokines and their specific receptors) is a promising direction for studies of genetic risk factors responsible for development of skin and joint inflammation in psoriasis and PsA. Immune disorders characterized by the deviation of cytokine profile by Th1-type (IL-2, IFNγ, TNFα) play a leading role in immunopathogenesis of
psoriasis and psoriatic arthritis. The review deals with analysis of publications regarding the role of cytokine gene polymorphisms associated with clinical course of psoriasis and PsA. Further search for genetic markers
determining clinical risks of PS and PsA would be an important step in personalized approach to prediction of occurrence and clinical course of the disease, as well as to arrangement of preventive measures, in order to prevent potential progression of the disease.
Autoantibodies are well-established biomarkers of autoimmune rheumatic diseases. Their detection in the routine clinical laboratory provides key information for early and differential diagnosis, prognosis, and monitoring of disease-activity. However, the currently existing variety of laboratory tests and methods as well as different diagnostic and clinical algorithms of autoimmune testing is the reason for lack of reproducibility and harmonization across immunological laboratories. Novel technical developments in the area of digital analysis of immunofluorescent images paved the way for the improvement of intra- and interlaboratory standardizationof test results. Additionally, digital immunofluorescence analysis enables the simultaneous multiparametric combination of cell- or tissue-based indirect immunofluorescence screening tests with confirmatory testing employing microparticles covered with purified autoantigens in one reaction environment.
ORIGINAL ARTICLES
The article presents some data concerning antigenic and immunogenic properties of the lethal heat-stable toxin (HST) from Yersinia pseudotuberculosis, a protein with molecular weight of 45 kDa. The mice,
following double immunization with HST at a dose of 0.1 mg per mouse, displayed higher antibody production, in comparison with a dose of 0.01 mg/mouse. The appropriate differences were revealed with regard of
leukocyte responses, i.e., development of leukopenia, neutropenia, lymphopenia upon immunization with the 0.01 mg of HST per mouse, whereas leukocytosis, and increase in lymphocytes and monocytes was detected after a dose of 0.1 mg/mouse. We detected some doseependent differences in cytokine-modulating activity. I.e., at HST dose of 0.01 mg per mouse, we detected mostly proinflammatory, acutehase responses, whereas a dose of 0.1 mg/mice caused induction of . IFNγ and cytokines promoting lymphocyte proliferation and antibody production by day +17. Upon double immunization of mice, the toxin showed protective properties when injecting them with lethal dose of Y. pseudotuberculosis. A lagging activation of antibody producers during
HST response suggests a need for searching effective adjuvant tools of enhancement and acceleration of specific humoral immune reactions against this antigen.
The article presents the results of studies concerning secretion of cytokines belonging to interleukin 12 family, i.e., IL-12р70, IL-12р40, IL-12р35 and IL-27 in mononuclear blood leukocytes, as well as expression of their specific receptors on T-lymphocytes from tuberculosis patients under the in vitro conditions of directed (resp., antigen- and cytokine-mediated) cell induction. In patients with pulmonary TB, we have registered suppression of both spontaneous and BCG-induced secretion of IL-12р70 and IL- 12р35, along with overproduction of IL-12р40 and IL-27. Furthermore, a decrease in relative contents of СD3+gp130+,CD3+IL12Rβ2+ lymphocytes were revealed in the in vitro IL-12/IL-27 induction tests, as well as increased concentration of T-cells with high expression of the inhibitory molecule WSX-1 (CD3+WSX-1+hi). It was shown that the detectable changes are unidirectional in most cases, being dependent on clinical form of the disease and sensitivity of the etiological agent to anti-tuberculosis drugs.
A comparative in vitro study of blood mononuclear cells from multiple sclerosis patients and healthy donors was performed, in order to evaluate proliferative response to a retroviral antigen, aiming to determine immunomodulatory properties of synthetic oligopeptide homologous to a highly conserved human endogenous retrovirus HERV-Eλ4-1 envelope protein. It was revealed that this oligopeptide is able to stimulate the in vitro spontaneous and mitogen-induced proliferation of blood mononuclear cells from either donor and multiple sclerosis patients. Intensity of this oligopeptide-induced stimulatory effect depends on the protein concentration, and on initial level of blood immunocompetent cells proliferation. Hence, the endogenous retrovirus HERV-Eλ4-1 envelope region protein is able to increase functional activity of immunocompetent cells from human blood, that suggesting its immunostimulatory properties. It is possible that the mitogenic effects of this protein upon immunocompetent cells of multiple sclerosis patients represent a potential mechanism of retroviral involvement into pathogenesis of the disorder.
Functional disorders of immune system are among potential reasons of periodontal disease, thus contributing to persistence of inflammatory infiltrate in periodontal tissues and resulting into chronic local inflammation. Disturbances of local and systemic immunity play an important role in the development of periodontitis. Local immunoreactivity is associated with the induced expression of proinflammatory cytokines and attraction of pro-inflammatory cells. Systemic disorders are associated with changes in T-helper cell subpopulations, as well as those of CD3-CD8+ lymphocytes. Severity of inflammatory events and clinical course of periodontal disease is determined by qualitative and quantitative content of the T-helper cells, that express CD45RA and CD45RO antigens. Composition of T cell subsets shows direct correlations with cytokine profile in blood serum and crevicular fluid from gingival pockets. A higher IL-17 concentration, as well as increased IFNγ and IL-18 levels in blood serum of the patients suggest a potential autoimmune mechanism in periodontitis. Upon emergence and development of periodontitis, an important role may be ascribed to ‘osteocluster’ cytokines (sRANKL and OPG), and detecton of their relative contents in crevicular fluid may be proposed for testing, in order to predict clinical risks in periodontitis.
The goal of present study was to perform a comparative evaluation of cytokine levels in blood of 123 patients with uncomplicated influenza versus a group of cases complicated by subsequent pneumonia. Higher levels of TNFα, IL-10, IL-6, IL-8 and lower levels of IFNγ were found in blood serum of those patients who developed pneumonia during acute phase of influenza. We have revealed a correlation between the severity and duration of symptoms of both uncomplicated and pneumonia-conplicated flu, and serum concentrations of proinflammatory (TNFα, IL-1β, IL-6, IL-8) and anti-inflammatory cytokines (IL-1rа, и IL-10), as well as with indexes of interferon profile (antiIFNα, IFNα и IFNγ) in the patients.
Blood levels of tumor necrosis factor-α (TNFα) and interferon γ (IFNγ) are shown to be increased in patients with rheumatoid arthritis, as compared to normal values. An increase of TNFα levels is shown to correlate with higher activity of inflammatory process, as well as with extra-articulate lesions in patients. Concentration of IFNγ proved to be significantly connected with activity of inflammatory process, and at later terms of the disorder ( > 1 year). TNFα and IFNγ levels are interconnected with joint lesions and functional scores of patients with rheumatoid arthritis.
We have observed forty-four patients with metastatic renal cancer before and after interferon therapy. Immune markers of of peripheral blood lymphocytes were determined by flow cytometry. Activity of NAD (P)-dependent dehydrogenase in blood lymphocytes was studied by means of bioluminescence technique. Changes of immune marker profiles and enzymatic activities of peripheral blood lymphocytes were found in patients with renal cancer after a course of interferon therapy.
SHORT COMMUNICATIONS
A complex clinical study included twenty patients with gastric cancer (tumor stage II) before and after surgical treatment, and 30 healthy volunteers, under appropriate informed consent. In patients with gastric cancer, we have revealed some changes of immunoregulatory peptides in blood serum that showed correlations with histological types of the tumors. Maximal baseline (pre-surgery) levels of interleukins (IL- 1β, IL-2, IL-4, IL-10) were found in highly differentiated adenocarcinoma, whereas IL-17, interferon (IFNγ) were more expressed in low differentiated carcinoma. TNFα levels were independent on histological type of the tumor. Following surgical treatment, serum concentrations of IL-1β, IL-2, IL-10 were found to be increased, along with decrease in IL-4, IL-17, IFNγ, TNFα. Following surgical treatment of gastric cancer, no septic complications were observed in the patients during the follow-up period. Our results indicate to usefulness of cytokine profile data in patients with gastric cancer during their treatment, taking into account a histological type of the tumor, in order to predict clinical course following surgical treatment.
The aim of this work was to compare clinical features of severity and some basic indicators of immune state in the patients with chronic recurrent furunculosis (CRF), differing in levels of serum immunoglobulin E (IgE). In cases with increased IgE levels, the clinical course proved to be more severe, as characterized by persistent recurrence of infection, with multiple lesions and weak inflammatory reaction, as compared with patients with normal IgE levels. Meanwhile, additional purulent skin lesions were less common among patients from this group. Comparative evaluation of basic anti-pyogenic defense effects allowed us to show a significant decrease of induced chemiluminescence of whole heparinized blood (p < 0.05) in patients with increased IgE levels, thus regarding it as a potential factor of more severe CRF clinical course in this cohort of patients.
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