Hungarian Immunology

[Altered rate and absolute count of Th1/Th2 and Tc1/Tc2 lymphocytes in whole blood of patients with psoriasis]

ANTAL-SZALMÁS Péter, ALEKSZA Magdolna, GONDA Andrea, HERÉDI Emese, SIPKA Sándor, HUNYADI János, SZEGEDI Andrea

OCTOBER 20, 2007

Hungarian Immunology - 2007;6(05)

[BACKGROUND - Psoriasis is a chronic inflammatory skin disorder characterised by an altered rate of interferon (IFN)-γ and interleukin (IL)-4 producing lesional and peripheral blood CD4+ and CD8+ T cells. To further characterise the imbalance of these cells and cytokines the rate and as a novel approach the absolute cell count (ACC) of IFN-γ+, IL-4+ and IL-10+ Thelper and Tcytotoxic cells was determined in the peripheral blood of psoriatic individuals. MATERIALS AND METHODS - Cell-associated cytokine expression was determined using intracellular cytokine staining and flow cytometry, serum cytokine levels were measured by enzyme linked immunosorbent assays (ELISAs) in the samples of 35 psoriatic patients and 15 controls. RESULTS - Significantly elevated rate (p<0.008) and ACC (p<0.009) of CD4+/IFN-γ+ cells was observed in the patients (28.3±8.8% and 237,216±134,154 cells/ml) compared to the healthy controls (21.0+ 6.8% and 135,772±50,212 cells/ml). In contrast the rate and the ACC of CD4+/IL-4+ cells decreased significantly in psoriasis (0.45±0.67% vs. 1.01± 0.48%, p<0.0001; 3,229±3,724 vs. 5,117±4,171 cells/ml, p<0.05). In the case of CD8+ T cells only the rate and the ACC of CD8+/IL-10+ cells increased significantly in patients compared to controls (5.49±5.42% vs. 1.59±0.78%, p<0.003 and 19,799±17,412 vs. 5,564±2,794 cells/ml, p<0.03). Though higher IFN-γ and lower IL-4 and IL-10 serum concentrations were detected in psoriasis these differences between patients and controls were not significant. Comparing the different cytokine parameters the serum cytokine levels showed some correlation only with the ACC and not with the rate of cytokine positive cells. CONCLUSIONS - These results further prove the presence of an altered balance in cytokine regulation towards the Thelper 1 cytokines in psoriasis, besides indicate that application of the ACC of cytokine positive helper and cytotoxic T cells as a novel parameter can help in the characterisation of these changes in different disorders.]

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Hungarian Immunology

[Examination of leukocyte-endothel interactions in inflammatory animal models]

GONDA Andrea, MIKECZ Katalin, HUNYADI János

[Leukocyte influx into tissues is one of the hallmarks of physiological reactions to inflammatory stimuli, which is followed by a multistep process, resulting in leukocyte extravasation from the postcapillary venules. The different kinds of adhesion molecules, that play role in the rolling and firm adhesion of the leukocytes, have been investigated very intensively. By the help of animal models of inflammation, numerous individuals, being in the same stage of the disease, can be examined. The requirement for the adhesion molecules for inflammatory responses could be investigated with antibodies or, nowadays more often, gene knock out (KO) or transgenic mice. Beside evaluating the morphological and cytokine profile differences, using intravital microscopy is of great importance in the inflammatory experiments, while it allows observing interactions of virtually any blood cell types with the endothelial wall in vivo. The results are sometimes conflicting, indicating that the process of leukocyte-endothel interactions depends on different kind of other factors than the adhesion molecules, and still not fully understood.]

Hungarian Immunology

[EULAR 2007]

SZEKANECZ Zoltán

Hungarian Immunology

[Waiting for DROP]

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Hungarian Immunology

[The role of endothelial cells]

CERVENAK László

[The role of endothelial cells is much beyond the well known barrier function between blood and tissues. Several different stimuli converge in the endothelial cells, which in turn regulate a number of vital processes in the organisms. Among these processes one of the most important is the immune response. Endothelial cells modulate the homing of leukocytes by the production of adhesion molecules and cytokines depending on activation state, anatomic location and vessel type. Endothelial cells express MHC and costimulatory molecules, which enables them to present antigens to T cells. Antigen presentation may lead to activation or tolerance of T cells depending on the phenotype of endothelial cells. They also express complement regulatory molecules and produce several complement cascade proteins. Endothelial cells take part in the catabolism of immunoglobulins as well as in the removal of circulating immune complexes. Finally, endothelial cells regulate inflammation at different levels by several mechanisms, which may substantially determinate the progression of the immune response.]

Hungarian Immunology

[Alpha calcidol treatment in patients with psoriatic arthropathy: clinical and immunological effects]

GAÁL János, LAKOS Gabriella, ALEKSZA Magdolna, KISS Judit, HORVÁTH Irén, HORKAY Edit, NAGY Georgina, SZEGEDI Andrea

[OBJECTIVE - Our objective was to describe the functional changes of the immune system also to evaluate the clinical parameters during systemic alphacalcidol (1αOH vitamin D3) treatment in patients with psoriatic arthropathy. PATIENTS AND METHOD - Nineteen patients with peripheral polyarticular form of psoriatic arthropathy were investigated. Ten patients were treated with daily 2×25 mcg alphacalcidol per os for 6 months and the other 9 patients served as controls. Three visits (at start, 3 and 6 months later) were carried out during the study, changes in the laboratory and clinical parameters were examined and analysed statistically in the treated and control groups. RESULTS - In the peripheral blood of the treated group a statistically significant decrease in the percentage of CD3/CD69 positive activated and CD8 positive IFNγ producing T cells was observed and the serum level of IFNγ also showed a significant decrease during the first 3 months. Another three months later no change in the above mentioned variables could be detected. Additionally, there was a significant decrease in the clinical activity of the disease using DAS28 score during the whole 6 months follow up period. In the control group no significant changes were observed. CONCLUSION - Our results show that systemic alphacalcidol treatment has a notable immune modulatory effect on patients with psoriatic arthropathy. This effect is manifested in short-term temporary decrease of type 1 immune responses and continuous decrease in the disease activity.]

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[Investigation of activated T-cells by non-Hodgkin’s lymphoma patients]

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[BACKGROUND - The immune system has several mechanisms to fight against developing malignant cell clones in the host, one of them is the activated T-cell response. Both CD4+ helper and CD8+ cytotoxic T-cells bear CD69 and HLA-DR molecules as important surface activation markers. AIM - Our aim was to determine, how the ratio of activated T-cells change in the peripheral blood of non-Hodgkin-lymphoma patients during the periods of polychemotherapy. PATIENTS AND METHODS - We used the peripheral blood samples of 43 non-Hodgkin-lymphoma’s patients (20 females, 23 males, mean age 52.4 years). We determined the level of CD3+/HLADR+ and CD3+/CD69+ T-cell subsets before, during and after the periods of polychemotherapy, using the methods of immunofluorescence stain and flow cytometry. RESULTS - We found the ratio of CD3+/HLA-DR+ cells significantly higher in non-Hodgkin-lymphoma’s patients before treatment compared to healthy controls (10.63% vs. 2.97%, p<0.001). During the period of polychemotherapy, this ratio began to increase significantly (16.94% vs. 10.63%, p=0.006). The level of CD3+/CD69+ cells did not change significantly. After treatment, the ratio of activated T-cells decreased, however, we detected significantly higher rate of CD3+/HLA-DR+ lymphocytes in patients who relapsed within one year than in those who stayed in remission (9.55% vs. 20.62%, p<0.001). CONCLUSION - Investigation of CD3+/HLA-DR+ activated T-cells might be a promising method to determine the immune defence and this way the prognostics of lymphoma patients.]

Hungarian Immunology

[Immune-dysfunctions in patients with Hodgkin’s lymphoma being in a long lasting complete remission]

ALEKSZA Magdolna, KERESZTES Katalin, BARÁTH Sándor, SIPKA Sándor, ILLÉS Árpád

[OBJECTIVES - Immunosuppression has long been known to be associated with Hodgkin’s lymphoma. The authors report on immunologic abnormalities with special focus on cellular immunity in patients with Hodgkin’s disease in complete remission. METHODS - We determined the proportion of the lymphocytes subpopulations, activated T cells, CD4+/CD25+ suppressor T cell population and intracytoplasmic cytokines by flow cytometry. The soluble cytokines were measured by classical ELISA technique. RESULTS - Based on lymphocyte cell surface antigen expression the subpopulations were as described in the literature, however a unique elevation of CD4+/CD25+ cell fraction was detected. The decreased amount of IFN-γ in the serum suggest Th2 dominance, but reduced intracellular IL-4 production in both CD4+ and CD8+ cells results from Th1 dominance. These results somewhat contrary but can not be completely compared as in vivo and in vitro techniques used for the analysis are not identical. However a constant elevation concentration and expression of IL-10 and TGF-β is observed. CONCLUSION - These alterations may reflect the existence of an immunosuppressive state also in the peripheral blood of Hodgkin’s lymphoma patients not only in the lymph nodes.]

Clinical Neuroscience

[IMPORTANCE OF THE ANALYSIS OF NEUTRALIZING ANTIBODIES TO IMMUNOMODULATORY THERAPY DURING TREATMENT OF MULTIPLE SCLEROSIS]

SERES Erika, VÉCSEI László

[Interferon-α, -β, and -γ have been used for the management of several diseases with varying clinical effects. Like many other proteins, all interferon species are potentially immunogenics especially those produced by recombinant gene technologies. A reliable screening assay for anti-interferon-β antibodies is suggested for patients with multiple sclerosis receiving interferon-β therapy. Natural interferon-β is a glycosylated 166 amino acid 25 kDa protein, recombinant interferon-β is available for therapy as 1a and 1b products. Both preparations induce anti-interferon-β antibodies, detectable in the serum of interferon-β-treated patients with multiple sclerosis. The question of wich assay is optimal for testing for antiinterferon- β antibodies in interferon-β-treated patients is unsettled. Two types of antibody assays are generally used: those measuring binding antibodies and those measuring neutralizing antibodies. The findings suggest that high titers of both binding and neutralizing antibodies reduce the clinical efficacy of interferon-β in relapsing-remitting multiple sclerosis, which is important for the long-term efficacy of these drugs. Treatment with glatiramer acetat has also been shown to induce the development of “reactive antibodies” in patients with multiple sclerosis. This article briefly describes some of the findings concerning anti-interferon binding and neutralizing antibodies.]

Hungarian Immunology

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Hungarian Immunology

[Immunophenotyping of mature cell non-Hodgkin’s lymphomas with leukemic clinical manifestation - newer approaches]

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[Immunophenotyping is commonly used in evaluating malignancies of the lympho-hemopoietic system and its use in various disease states of mature lymphoid leukemias and related non-Hodgkin’s lymphomas is reviewed here. The major goals of immunophenotyping in mature lymphoid neoplasias are the assignment of abnormal cells to the B or T/NK linkage, their maturational analysis, and the characterization of specific phenotypes which might be helpful for the subclassification of disease. There is not known, however, any lymphoma (leukemia) -specific antigen and the individual type of lymphoid leukemias and lymphomas does not follow the antigen expression profile of normal differentiation. Therefore, the approach to analysis of lymphoid neoplasias requires thoughtful utilization of laboratory testing, in order to meet both medical and economic goals of the laboratory and caregivers. The interpreter should expect to see a pattern of both positive and negative immunoreactivities that is appropriate to the final interpretation. The value and type of information provided by immunophenotyping in these malignancies varies and this paper outlines approaches for clinicians and laboratorians to follow when reviewing clinical data. The future for this technology is outstanding because it is the only one available today that can both rapidly and accurately measure multiple correlated cell properties. However, combined clinical-laboratory approach to diagnosis and prognostication seems to be important including traditional and newer (molecular genetic, molecular biology) methodologies.]