Andrea Szegedi

Publications of Andrea Szegedi

• Altered peripheral invariant natural killer T cells in atopic dermatitis.

  Authors: Edit Gyimesi, Georgina Nagy, Éva Remenyik, Sándor Sipka, Margit Zeher, Tamás Bíró, Andrea Szegedi

  Journal of clinical immunology. 06/2011; 31(5):864-72.

  Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. The frequency and number ofConflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4- subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining. The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4-CD8- (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls. The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.

• Association between serum IL-16 levels and the degree of sensitization in patients with atopic dermatitis.

  Authors: Georgina Nagy, Krisztián Gáspár, Beatrix Irinyi, Mónika Gál, Judit Tumpek, Edit Gyimesi, Sándor Sipka, Éva Remenyik, Péter Szodoray, Andrea Szegedi

  International archives of allergy and immunology. 03/2011; 156(1):69-74.

  Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. OurInterleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization.

• Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets.

  Authors: Bertalan Mesko, Szilard Poliska, Andrea Szegedi, Zoltan Szekanecz, Karoly Palatka, Maria Papp, Laszlo Nagy

  BMC medical genomics. 01/2010; 3:15.

  Chronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, butChronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood. It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other. Diseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05). Here we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition. These findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.

• Immunological and Clinical Effects of Alphacalcidol in Patients with Psoriatic Arthropathy: Results of an Open, Follow-up Pilot Study.

  Authors: János Gaál, Gabriella Lakos, Péter Szodoray, Judit Kiss, Irén Horváth, Edit Horkay, Georgina Nagy, Andrea Szegedi

  Acta dermato-venereologica. 02/2009; 89(2):140-4.

  The aim of this study was to describe the effect of systemic alphacalcidol (1 OH vitamin D3) treatment on clinical and immunological parameters in patients with psoriatic arthropathy. Among the 19The aim of this study was to describe the effect of systemic alphacalcidol (1 OH vitamin D3) treatment on clinical and immunological parameters in patients with psoriatic arthropathy. Among the 19 patients investigated, 10 were treated with 0.25 microg oral alphacalcidol twice daily for 6 months, while 9 other patients served as controls. In the peripheral blood of the treated group but not in the controls, a statistically significant decrease was observed in the percentage of CD3/CD69-positive activated and CD8-positive interferon- -producing T cells and in the serum level of interferon- during the first 3 months and also in the clinical activity of the disease during the whole 6-month follow-up period. Our results show that systemic alphacalcidol treatment has an immunomodulatory effect on patients with psoriatic arthropathy. This effect is manifested by a short-term temporary decrease in type 1 immune responses and a continuous decrease in disease activity. Key words: alphacalcidol treatment; psoriatic arthropathy; immunomodulatory effect.

• Protein kinase C isoenzymes differentially regulate the differentiation-dependent expression of adhesion molecules in human epidermal keratinocytes.

  Authors: Andrea Szegedi, Edit Páyer, Gabriella Czifra, Balázs I Tóth, Emese Schmidt, László Kovács, Peter M Blumberg, Tamás Bíró

  Experimental dermatology. 02/2009; 18(2):122-9.

  Epidermal expression of adhesion molecules such as desmogleins (Dsg) and cadherins is strongly affected by the differentiation status of keratinocytes. We have previously shown that certain proteinEpidermal expression of adhesion molecules such as desmogleins (Dsg) and cadherins is strongly affected by the differentiation status of keratinocytes. We have previously shown that certain protein kinase C (PKC) isoforms differentially alter the growth and differentiation of human epidermal HaCaT keratinocytes. In this paper, using recombinant overexpression and RNA interference, we define the specific roles of the different PKC isoenzymes in modulation of expression of adhesion molecules in HaCaT keratinocytes. The level of Dsg1, a marker of differentiating keratinocytes, was antagonistically regulated by two Ca-independent 'novel' nPKC isoforms; i.e. it increased by the differentiation-promoting nPKCdelta and decreased by the growth-promoting nPKCepsilon. The expression of Dsg3 (highly expressed in proliferating epidermal layers) was conversely regulated by these isoenzymes, and was also inhibited by the differentiation inducer Ca-dependent 'conventional' cPKCalpha. Finally, the expression of P-cadherin (a marker of proliferating keratinocytes) was regulated by all of the examined PKCs, also in an antagonistic manner (inhibited by cPKCalpha/nPKCdelta and stimulated by cPKCbeta/nPKCepsilon). Collectively, the presented results strongly argue for the marked, differential, and in some instances antagonistic roles of individual Ca-dependent and Ca-independent PKC isoforms in the regulation of expression of adhesion molecules of desmosomes and adherent junctions in human epidermal keratinocytes.

• Clinical and laboratory examinations in the subgroups of chronic urticaria.

  Authors: Beatrix Irinyi, György Széles, Edit Gyimesi, Judit Tumpek, Emese Herédi, Georgitsis Dimitrios, Róza Adány, János Hunyadi, Andrea Szegedi

  International archives of allergy and immunology. 02/2007; 144(3):217-25.

  BACKGROUND: The aetiology of chronic urticaria is heterogeneous. Physical urticaria (PU) is estimated at around 35%, autoimmune urticaria (AIU) at 25% and chronic idiopathic urticaria (CIU) at 35% ofBACKGROUND: The aetiology of chronic urticaria is heterogeneous. Physical urticaria (PU) is estimated at around 35%, autoimmune urticaria (AIU) at 25% and chronic idiopathic urticaria (CIU) at 35% of all chronic urticaria cases. METHODS: Differences in clinical and laboratory parameters among AIU, PU and CIU groups were examined. AIU was diagnosed if the basophil CD63 assay was positive. Demographic data, severity of symptoms and association with allergic and autoimmune diseases were analysed by the aid of a questionnaire. Immunoassays were carried out and the effectiveness of therapy was also investigated. RESULTS: Concerning the urticaria score, AIU patients had significantly higher total urticaria scores than patients with CIU (p = 0.013), dermatographic urticaria (p = 0.05) or cholinergic urticaria (p = 0.038). Between CIU and dermatographic urticaria and between CIU and cholinergic urticaria patients, we found insignificant differences in the urticaria score (p = 0.707 and p = 0.336, respectively). AIU was more frequently associated with autoimmune diseases in the personal history (p < 0.001) and with other types of urticaria in the family history (p < 0.001). Also, anti-thyroid antibodies were more frequently detected in the AIU group. Antihistamine therapy was less effective in the AIU group (12.8%) than in the PU (70.3%) and CIU groups (68.6%), but there were no significant differences between the CIU and PU groups regarding the effectiveness of antihistamine therapy. CONCLUSION: The autoimmune subgroup represents the most severe form of chronic urticaria. On the other hand, there were no significant differences between the CIU and PU groups neither in urticaria scores nor in response to antihistamine therapy.

• Analysis of components of the CD14/TLR system on leukocytes of patients with atopic dermatitis.

  Authors: Andrea Sümegi, Andrea Szegedi, Mónika Gál, János Hunyadi, Gyula Szegedi, Péter Antal-Szalmás

  International archives of allergy and immunology. 02/2007; 143(3):177-84.

  BACKGROUND: Atopic dermatitis (AD) is frequently associated with skin infections that may be a consequence of an impaired function of the innate immune response. Conversely, the frequent bacterialBACKGROUND: Atopic dermatitis (AD) is frequently associated with skin infections that may be a consequence of an impaired function of the innate immune response. Conversely, the frequent bacterial colonization may also influence the systemic immune reactions, including the Toll-like receptor (TLR) system, through the translocation of bacterial components into the circulation. Therefore, we characterized phenotypic and functional properties of the TLR system in patients with extrinsic and intrinsic AD. METHODS: The absolute number of surface CD14, TLR2, TLR4 and CD180 and the CD14-mediated uptake of bodipy-labeled endotoxin and bacteria by whole blood leukocytes was studied by flow cytometry. We measured the serum soluble CD14 concentration by an inhibitory flow cytometric method. RESULTS: We observed a significant overexpression of TLR2 and TLR4 on monocytes, TLR2 and CD14 on granulocytes and CD180 on lymphocytes of intrinsic AD patients compared to healthy controls. The serum soluble CD14 was not different in the intrinsic AD patients, while it was diminished in the extrinsic AD group compared to the controls. The endotoxin and bacterium uptake showed no differences. CONCLUSIONS: The observed upregulation of CD14, TLR2, TLR4 and CD180 on peripheral leukocytes seems to be rather a consequence than the cause of the repeated bacterial infections in AD.

• [Interferon induced psoriatic arthritis in a patient with renal cancer]

  Authors: János Gaál, Judit Kálmánchey, Andrea Szegedi, Bela Szabó, Péter Surányi

  Orvosi hetilap. 01/2006; 146(49):2503-6.

  Interferon induced psoriatic arthritis in a patient with renal cancer. The authors describe a patient's history, whose alpha interferon treatment was started after the nephrectomy because of renalInterferon induced psoriatic arthritis in a patient with renal cancer. The authors describe a patient's history, whose alpha interferon treatment was started after the nephrectomy because of renal tumor spreading into the inferior caval vein. One week after the starting the interferon treatment typical psoriatic plaques and acute polyarthritis developed with prominent inflammatory signs. The cessation of interferon treatment, administration of systemic and intraarticular steroid, non steroid antiinflammatory drug and combined disease modifying drug therapy resulted in termination of skin symptoms and definitive relief in articular complaints. Moreover there were found laboratory alterations characteristic for autoimmune thyroiditis as well. The authors attributed both manifestations to rare immunological side effects of interferon treatment and survey the relevant literature.

• High prevalence of oesophageal involvement in patients with undifferentiated connective tissue disease using radionuclide oesophageal transit scintigraphy.

  Authors: János Gaál, József Varga, Lajos Szabados, Ildikó Garai, László Galuska, Péter Surányi, Andrea Szegedi, Margit Zeher, Edit Bodolay

  Nuclear medicine communications. 01/2006; 26(12):1113-7.

  AIM: To look for the frequency of oesophageal dysfunction using radionuclide oesophageal transit scintigraphy in 145 patients with undifferentiated connective tissue disease (UCTD); to seek theAIM: To look for the frequency of oesophageal dysfunction using radionuclide oesophageal transit scintigraphy in 145 patients with undifferentiated connective tissue disease (UCTD); to seek the correlation between the clinical/laboratory data and scintigraphic alterations; and to determine predictive value of radionuclide oesophageal transit scintigraphy for evolution to established connective tissue disease (CTD). METHOD: One hundred and forty-five patients with UCTD were examined by 99mTc-DTPA oesophageal transit scintigraphy. The intraoesophageal transport of the radiopharmaceutical was followed and imaged by a gamma camera, a series of 128 x 128 images were stored and evaluated. The correlation between the scintigraphic data and clinical and laboratory parameters was analysed statistically. RESULTS: Unequivocally positive scintigraphy, indicative of motor abnormality was found in 46% of patients (66), 71% (47) of whom were totally asymptomatic. Significant correlation was found between the presence and severity of scintigraphic alterations and antinuclear antibodies, the anti-beta2GPI, IgM, IgG, the aCL antibody positivity, and the skin symptoms. Scintigraphic positivity was significantly more frequent in patients evolving to definitive CTD (P = 0.0178), and abnormal scan predisposed to transition into the definitive CTD (odds ratio, 2.292; CI, 1.610-4.525). Its cumulative positive predictive value was found to be 43% and cumulative negative predictive value 73% with regard to the development of a definitive CTD. CONCLUSION: Our results show that scintigraphic alterations together with clinical and laboratory alterations can help the clinician in the prediction of final outcome.

• D-penicillamine-induced pemphigus vulgaris in a patient with scleroderma-rheumatoid arthritis overlap syndrome.

  Authors: Andrea Szegedi, Péter Surányi, Gabriella Szücs, Mária Kiss, János Hunyadi, János Gaál

  Acta dermato-venereologica. 02/2004; 84(4):318-9.

• Immunohistochemical examination of P-cadherin in bullous and acantholytic skin diseases.

  Authors: Anikó Kovács, Emese Schmidt, Agnes Bégány, János Hunyadi, Andrea Szegedi

  Acta dermato-venereologica. 02/2004; 84(2):116-9.

  Autoimmune blistering diseases (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, dermatitis herpetiformis) and certain genodermatoses with acantholysis (Darier-disease, Hailey-HaileyAutoimmune blistering diseases (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, dermatitis herpetiformis) and certain genodermatoses with acantholysis (Darier-disease, Hailey-Hailey disease) have different aetiological factors, but all result in bulla formation and/or in acantholysis. Cadherins are Ca++-dependent cell-cell adhesion molecules which play an important role in the cellular connection between normal cells. P-cadherin is involved in the selective adhesion of epidermal cells, and is expressed only on the surfaces of the two basal layers. We examined the expression of P-cadherin in some autoimmune bullous skin diseases and Darier's disease using immunohistochemistry and found P-cadherin to be strongly upregulated. We believe the upregulation is compensatory to the primary pathophysiological events in the various bullous dermatoses.

• Elevated rate of Thelper1 (T(H)1) lymphocytes and serum IFN-gamma levels in psoriatic patients.

  Authors: Andrea Szegedi, Magdolna Aleksza, Andrea Gonda, Beatrix Irinyi, Sándor Sipka, János Hunyadi, Péter Antal-Szalmás

  Immunology letters. 05/2003; 86(3):277-80.

  Several disorders are known to be associated with altered Thelper1/Thelper2 (T(H)1/T(H)2) cytokine balance. Psoriasis is characterized by increased systemic and local production of T(H)1 andSeveral disorders are known to be associated with altered Thelper1/Thelper2 (T(H)1/T(H)2) cytokine balance. Psoriasis is characterized by increased systemic and local production of T(H)1 and pro-inflammatory cytokines. Furthermore recent data indicate the dominant presence of T(H)1 lymphocytes in the circulation and T(H)1 and Tcytotoxic1 (T(C)1) cells in lesional skin of psoriatic patients. In order to assess the systemic T(H)1/T(H)2 imbalance in psoriasis most of the studies so far tested isolated peripheral mononuclear cells. As a new approach we applied a whole blood flow cytometric assay to determine the rate of circulating T(H)1/T(H)2 and T(C)1/Tcytotoxic2 (T(C)2) lymphocytes based on their intracellular IFN-gamma, IL-4 and IL-10 expression. Besides, serum levels of these cytokines were determined in healthy controls and psoriatic patients by commercial ELISAs. In psoriatic patients we found significantly (P<0.02) increased rates of CD4(+)/IFN-gamma(+) lymphocytes (30.3+/-8.8%) while the percent of CD4(+)/IL-4(+) cells (0.37+/-0.31%) were significantly (P<0.03) lower compared to healthy controls (CD4(+)/IFN-gamma(+): 20.1+/-7.3% and CD4(+)/IL-4(+): 0.78+/-0.44%). The IL-10-positive CD4(+) and CD8(+) cells also had higher rate in psoriasis, but the difference between patients and controls was not significant, similarly to the rate of CD8(+)/IFN-gamma(+) and CD8(+)/IL-4(+) lymphocytes. Beside cellular expression, serum IFN-gamma levels were also significantly higher (control: 4.9+/-6.4 pg/ml; psoriatic patients: 35.9+/-47.0 pg/ml; P<0.05). Our results provide further evidence for an altered T(H)1/T(H)2 balance in psoriasis measured in non-separated whole blood T cells.

• Serum cytokine levels and type 1 and type 2 intracellular T cell cytokine profiles in mixed connective tissue disease.

  Authors: Edit Bodolay, Magdolna Aleksza, Péter Antal-Szalmás, Judit Végh, Péter Szodoray, Pál Soltész, Andrea Szegedi, Zoltán Szekanecz

  The Journal of rheumatology. 10/2002; 29(10):2136-42.

  OBJECTIVE: To determine serum cytokine concentrations and intracellular cytokine production of CD4+ and CD8+ T cells in 20 patients with mixed connective tissue disease (MCTD). METHODS: DetailedOBJECTIVE: To determine serum cytokine concentrations and intracellular cytokine production of CD4+ and CD8+ T cells in 20 patients with mixed connective tissue disease (MCTD). METHODS: Detailed analysis of cytokine production; 8 patients were in the active stage, 12 in the inactive stage of the disease. Serum concentrations of interferon-gamma (IFN-gamma), interleukin 4 (IL-4), and IL-10 were assessed by ELISA. Intracellular content of IFN-gamma, IL-4, and IL-10 in CD4+ and CD8+ peripheral blood T cell and lymphocyte subsets was determined by flow cytometry. RESULTS: Serum concentrations of both type 1 and type 2 cytokines were significantly higher in patients with MCTD than in healthy controls. IFN-gamma expression of CD4+ and CD8+ T cells did not differ comparing all patients to controls. In patients with active MCTD, the percentage of CD8+/IFN-gamma+ Tc1 cells was significantly increased compared to inactive disease or to controls (p < 0.05). IL-4 expression of CD4+ T cells was scarcely detectable in MCTD, while a subpopulation of CD8+ Tc2 cells produced IL-4. A higher percentage of these CD8+/IL-4+ Tc2 cells were detected in patients with MCTD, especially in active disease, compared to controls (p < 0.05). The percentage of IL-10-expressing CD4+ and CD8+ T cells was higher in patients than in controls (p < 0.05). Again, CD4+ and CD8+ T cells from patients with active MCTD produced significantly more IL-10 than cells in patients with inactive disease or in controls (p < 0.05). CONCLUSION: Our results suggest that MCTD is associated with increased production of both type 1 (IFN-gamma) and type 2 cytokines (IL-4, IL-10). Cytokine production is usually higher in active MCTD than in inactive disease. CD8+ T cells may produce more IFN-gamma and IL-10 in comparison to CD4+ T cells. Patients with active disease have more IL-4-expressing Tc2 cells and IL-10-expressing Th2 and Tc2 cells than patients with inactive MCTD or controls. In MCTD, increased IL-10 production by Th2 and Tc2 cells may be an attempt by the immune system to downregulate the inflammatory reaction, although this effect may not be sufficient to restore the physiological Th1/Th2 balance in MCTD.

• [Amyopathic dermatomyositis]

  Authors: Katalin Dankó, Enikö Simkovics, Orsolya Nagymáté, Magdolna Aleksza, Andrea Szegedi

  Orvosi hetilap. 03/2002; 143(7):341-6.

  Dermatomyositis is a systemic autoimmune disease which belongs to the group of idiopathic inflammatory myopathies. The disease is rare with an incidence of 0.1-1/100,000 and a prevalence ofDermatomyositis is a systemic autoimmune disease which belongs to the group of idiopathic inflammatory myopathies. The disease is rare with an incidence of 0.1-1/100,000 and a prevalence of 1-6/100,000. Women are affected twice as often as men. In some patients the disease presents with dermatologic changes weeks to months before the myopathy arises. It was observed that in some patients the myositis develops much later and sometimes not at all. Therefore, the term of dermatomyositis sine myositis used in earlier literature has been changed to amyopathic dermatomyositis. The most important question is whether the patient needs systemic therapy with its possible side effects yet possibly preventing the appearance of myositis or only local therapy for the skin manifestations is necessary. The goal of this article is to summarize the latest findings in amyopathic dermatomyositis.

• Cytokine production of CD4+ and CD8+ peripheral T lymphocytes in patients with chronic idiopathic urticaria.

  Authors: Beatrix Irinyi, Magdolna Aleksza, Péter Antal-Szalmás, Sándor Sipka, Janos Hunyadi, Andrea Szegedi

  Acta dermato-venereologica. 02/2002; 82(4):249-53.

  The aim of this study was to investigate the characteristic cytokine pattern of patients with chronic idiopathic urticaria. Using flow cytometry, we examined the frequency of IL4, IL-10, IL-13 andThe aim of this study was to investigate the characteristic cytokine pattern of patients with chronic idiopathic urticaria. Using flow cytometry, we examined the frequency of IL4, IL-10, IL-13 and IFN-gamma producing CD4+ and CD8+ T cells in the peripheral blood mononuclear cells at a single cell level. In patients with chronic idiopathic urticaria, the frequency of IL-10 producing CD4+ and CD8 + T cells was significantly higher than that of control subjects, while the frequency of IFN-y producing helper and cytotoxic T cells was significantly lower. The proportion of IL-4 producing CD4 + T cells from patients with urticaria was significantly lower. The ratio of IL-4 producing CD8 + T cells and the proportion of IL-13 producing CD4 + and CD8 + T lymphocytes did not show any significant difference between patients and controls. In our study, we could observe neither a dominant Th1 nor a dominant Th2 type cytokine pattern. We found a significant elevation in the intracellular IL-10 level which may be the cause of the down-regulated Th1 and Tc1 and partly Th2 lymphocyte functions.

• Elevated rate of Thelper1 (TH1) lymphocytes and serum IFN-γ levels in psoriatic patients

  Authors: Andrea Szegedi, Magdolna Aleksza, Andrea Gonda, Beatrix Irinyi, Sándor Sipka, János Hunyadi, Péter Antal-Szalmás

  Immunology Letters.

  Several disorders are known to be associated with altered Thelper1/Thelper2 (TH1/TH2) cytokine balance. Psoriasis is characterized by increased systemic and local production of TH1 andSeveral disorders are known to be associated with altered Thelper1/Thelper2 (TH1/TH2) cytokine balance. Psoriasis is characterized by increased systemic and local production of TH1 and pro-inflammatory cytokines. Furthermore recent data indicate the dominant presence of TH1 lymphocytes in the circulation and TH1 and Tcytotoxic1 (TC1) cells in lesional skin of psoriatic patients. In order to assess the systemic TH1/TH2 imbalance in psoriasis most of the studies so far tested isolated peripheral mononuclear cells. As a new approach we applied a whole blood flow cytometric assay to determine the rate of circulating TH1/TH2 and TC1/Tcytotoxic2 (TC2) lymphocytes based on their intracellular IFN-γ, IL-4 and IL-10 expression. Besides, serum levels of these cytokines were determined in healthy controls and psoriatic patients by commercial ELISAs. In psoriatic patients we found significantly (P<0.02) increased rates of CD4+/IFN-γ+ lymphocytes (30.3±8.8%) while the percent of CD4+/IL-4+ cells (0.37±0.31%) were significantly (P<0.03) lower compared to healthy controls (CD4+/IFN-γ+: 20.1±7.3% and CD4+/IL-4+: 0.78±0.44%). The IL-10-positive CD4+ and CD8+ cells also had higher rate in psoriasis, but the difference between patients and controls was not significant, similarly to the rate of CD8+/IFN-γ+ and CD8+/IL-4+ lymphocytes. Beside cellular expression, serum IFN-γ levels were also significantly higher (control: 4.9±6.4 pg/ml; psoriatic patients: 35.9±47.0 pg/ml; P<0.05). Our results provide further evidence for an altered TH1/TH2 balance in psoriasis measured in non-separated whole blood T cells.

• AZ ANTIGÉNPREZENTÁLÓ SEJTEK, A REGULATÓRIKUS T SEJTEK ÉS AZ NKT SEJTEK VIZSGÁLATA ATOPIÁS DERMATITISBEN = CHARACTERIZATION OF ANTIGEN PRESENTING CELLS, REGULATORY T CELLS AND NKT CELLS IN ATOPIC DERMATITIS

  Authors: Andrea Szegedi, Péter Antal-Szalmás, Sándor Baráth, Mónika Gál, Edit Gyimesi, János Hunyadi, Georgina Husztiné Nagy, Imre Szabó

  Az atopiás dermatitis (AD) immunpatológiai eltéréseinek megismerését célzó kutatásaink során megállapítottuk, hogy míg a Tr1 sejtek száma szignifikánsan emelkedett volt AD betegek perifériás vérében,Az atopiás dermatitis (AD) immunpatológiai eltéréseinek megismerését célzó kutatásaink során megállapítottuk, hogy míg a Tr1 sejtek száma szignifikánsan emelkedett volt AD betegek perifériás vérében, a nTreg sejtek esetében sem a sejtszám, sem a funkció nem mutatott lényeges eltérést. Az AD gyulladásos bőrben ugyanakkor nagy számban mutattunk ki CD4+/CD25+/Foxp3+ nTreg sejteket. Elsőként közöltük, hogy akut AD epidermisben a dendritikus sejtek csoportokat alkotva helyezkednek el, melyekben szoros kapcsolat mutatható ki a dendritikus sejtek és a CD4+/CD25+/Foxp3+ T sejtek között. Fenotípusosan a sejtekre a CD1a+/CD11c+/CD40+/CD123-/CD207- felszíni molekula készlet volt jellemző. A betegek vérében mind az NKT sejtek százalékos aránya, mind pedig abszolút sejtszáma szignifikánsan csökkent. Először mutattuk ki, hogy a CD4-/CD8- NKT alcsoport szignifikánsan kevesebb IFN?-t és szignifikánsan több IL-4-et termel az egészséges kontrollokhoz képest. A perifériás vér fehérvérsejteken nem tudtuk a toll-szerű receptorok csökkent számát, vagy kóros funkcióját detektálni. Ezzel ellentétben szignifikánsan emelkedett számot találtunk, melyet következményes jellegűnek tartunk. Ezeken kívül kimutattuk, hogy AD-es betegekben a LTB4 szignál útvonal kifejezetten felerősödött egészségesekhez viszonyítva, valamint, hogy szignifikánsan magasabb a szérum IL-16 szintje, azonban ez kevésbé jelzi a szenzitizáció mértékét, mint a totál IgE szint. | Our research aimed to investigate the possible immunological alterations in atopic dermatitis (AD). While Tr1 cell number was significantly elevated in the peripheral blood of AD patients, nTreg cells showed no significant changes either in number or in function. Besides, in the inflamed AD skin CD4+/CD25+/Foxp3+ nTreg cells were detected in large amount. In the epidermis of acute AD skin the dendritic cells were located in clusters and there was a close connection between dendritic cells and the CD4+/CD25+/Foxp3+ T cells. Phenotypically the cells displayed a CD1a+/CD11c+/CD40+/CD123-/CD207- cell surface molecule feature. We found that the absolute number and percentage of NKT cells in the peripheral blood of AD patients were significantly decreased. We demonstrated that the CD4-/CD8- NKT subgroup produced significantly lower amount of IFN-gamma and significantly higher amount of IL-4 compared to healthy controls. We detected no evidence of decreased numbers or altered functions of toll-like receptors on the surface of peripheral blood leukocytes. On the other hand we detected significantly elevated number of these receptors that might be a consequential effect. Furthermore we demonstrated that the LTB4 signal pathway in AD patients was extremely powered compared to healthy volunteers, and that the serum IL-16 level was significantly elevated in AD serum that was correlated with the degree of sensitization at a lower extent than that of total serum IgE level.

• Thelper és Tcitotoxikus lymphocyták szerepének vizsgálata allergológiai és autoimmun bőrgyógyászati kórképekben = The role of Thelper and Tcytotoxic lymphocytes in allergic and autoimmune skin diseases

  Authors: Andrea Szegedi, Magdolna Aleksza, István Csípő, Katalin Dankó, János Hunyadi, Beatrix Irinyi

  Mind a T helper, mind a T citotoxikus limfociták csoportja szubpopulációkra osztható citokin termelésük alapján (Th1/Th2, Tc1/Tc2). Számos kutatói munka és klinikai vizsgálat felveti annakMind a T helper, mind a T citotoxikus limfociták csoportja szubpopulációkra osztható citokin termelésük alapján (Th1/Th2, Tc1/Tc2). Számos kutatói munka és klinikai vizsgálat felveti annak lehetőségét, hogy a szubpopulációk egymáshoz viszonyított kóros aránya és citokin termelése bizonyos kórképek kialakulásában patogenetikai szerepet játszhat. Ugyanakkor ma már tudjuk, hogy nem mindig lehet éles különbségeket megállapítani a szubpopulációk eloszlásában, valamint a betegség lefolyása során is változhat ez az arány. A most befejezett OTKA pályázat során sikerült számos új adatot nyernünk, melyek segítik az atopiás dermatitis, autoimmun krónikus urticaria (ACU), psoriasis vulgaris, polymyositis, dermatomyositis és kevert kötőszövet betegség patogenezisének jobb megismerését, elsősorban a perifériás vér T limfocita szubpopulációinak, az aktivált T sejtek, a Th1/Th2 és Tc1/Tc2 sejtek arányának, valamint a szérum szolubilis citokin szintjeinek vizsgálata révén. Ugyancsak tanulmányoztuk az UV-A1 fototerápia szisztémás lupus erytematosusban szenvedő betegekre kifejtett kedvező hatásának feltételezhető immunológiai hátterét, valamint új diagnosztikai módszert dolgoztunk ki az ACU laboratóriumi diagnosztikájára. Kimutattuk, hogy autoimmun hólyagos betegségekben a P-cadherin expressziója kompenzatórikusan fokozódhat, és hogy HaCat sejtekben az adhéziós molekulák megjelenése összefüggésben állhat a protein kináz C izoformák kifejeződésével. | Both T helper and T cytotoxic lymphocytes can be divided into subgroups according to their cytokine production (Th1/Th2; Tc1/Tc2). Clinical investigations and basic research studies raised the possibility, that abnormality in the ratio and cytokine production of these lymphocyte subpopulations can play a role in the pathogenesis of different diseases. On the other hand, it is also known, that strict differences cannot always be observed and the proportion of these subpopulations can change during the course of the disease. In the present work the pathogenesis of atopic dermatitis, autoimmune chronic urticaria (ACU), psoriasis vulgaris, polymyositis, dermatomyositis and mixed connective tissue disease were studied and we were able to get new data on the percentage of different T lymphocyte subgroups and activated T cells in the peripheral blood, on the ratio of Th1/Th2 and Tc1/Tc2 cells and also on the serum cytokine levels. The effects of UVA1 phototherapy on the immunological laboratory parameters of patients suffering from systemic lupus erythematosus were also investigated and a new method was developed for the diagnosis of ACU. In autoimmune blistering diseases we detected compensatorical upregulation of P-cadherin, and in HaCaT cells we found correlation between the expression of different adhesion molecules and protein kinase C isoforms.

• Az immuntolerancia vizsgálata autoimmun kórképekben = Investigations on the immune tolerance in autoimmune diseases

  Authors: Gyula Szegedi, Magdolna Aleksza, Edit Bodolay, Boglárka Csilla Brúgós, Katalin Dankó, Edit Gyimesi, Emese Kiss, Sándor Sipka, Andrea Szegedi, Zoltán Szekanecz, Tünde Tarr, Margit Zeher

  A "nem differenciált collagenosis-ban" (NDC-ben) a korai diagnózisra, hatékonyabb kezelésre és gondozásra alkalmas immunológiai és szervi eltéréseket mutattunk ki. A primer és szekunderA "nem differenciált collagenosis-ban" (NDC-ben) a korai diagnózisra, hatékonyabb kezelésre és gondozásra alkalmas immunológiai és szervi eltéréseket mutattunk ki. A primer és szekunder anti-foszfolipid szindróma kutatásának folytatása során az SLE-s betegekben egy elkülönült fenotipust írtunk le. Az SLE-s betegek 5 éves követése alapján terápiás ajánlást fogalmaztunk meg. A regulatív T sejtek (CD+CD25+ FoxP3, CD4+IL-10+) számbeli és funkcionális jellemzését vizsgáltuk különböző poliszisztémás betegségekben. A poliszisztémás autoimmun betegségben (SLE, MCTD, PSS, RA, NDC-ben) szenvedő betegekben kardiovaszkuláris állapot felmérést végeztünk. Az endothel sejtek funkcionális státuszára utaló in vivo mérésekkel korai károsodásokat rögzítettünk, amik összefüggtek az immunológiai eltérésekkel. A pulmonáris hipertoniás, MCTD-s betegekben az anti-endothel autoantitestek patogenetikai szerepét feltételezzük. Új adatokat szolgáltattunk a kortikoszteroidok, D3 vitaminok és a plazmaferezis hatásmechanizmusához az autoimmun betegekben. Bizonyítottuk az UV-A1 fototerápia hatásosságát SLE-ben, és hazánkban elsőként vezettük be az autolog CD34+őssejt terápiát a poliszisztémás betegek kezelésében | We have found immunological and organic alterations suitable for the early diagnosis, more efficient treatment and following up of the patients with 'non differenciated collagenosis' (NDC). During the continuation of the research on primary and secondary anti-phospholipid syndrome, a new phenotype of this disease could be observed in the patients with SLE. An useful therapeutic protocol was composed on the basis of a 5 years long following up study on SLE patients. The quantitative and functional characterizations of the regulative (CD+CD25+Foxp3+, CD4+IL-10+) T cells were carried out in various autoimmune diseases. We analysed the actual cardiac state in the patients with polysystemic autoimmune disease (in SLE, MCTD, PSS, RA, NDC). By the in vivo methods used for the functional testing of endothelial cells, we could record some early alterations connected with the immunological impairments. We suppose the pathogenic role of anti-endothelial autoantibodies in MCTD patients suffering from pulmonary hypertension. New data were presented for the ways of action of corticosteroids, vitamines D3 and the plasmapheresis in autoimmune patients. The efficacy of UV-A1 phototherapy was proven in SLE. We started the first autologous CD34+ stem cell transplantation therapy for polysystemic autoimmune patients in Hungary.