Beatrix Irinyi

University of Debrecen, Debreczyn, Hajdú-Bihar, Hungary

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Publications (18)37.18 Total impact

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    ABSTRACT: Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations. Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in AD patients. We introduced a novel classification of AD patients based on FLG mutations and SCORAD. Based on these parameters, we created three groups of AD patients: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C) patients. In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses. Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitisation-specific parameters. These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in FLG mutant and wild-type AD patients with severe symptoms. Nevertheless, our results also suggest that FLG mutant patients may have a higher risk of allergic sensitisation compared to wild-type patients. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 11/2013; · 3.76 Impact Factor
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    ABSTRACT: Chronic urticaria (CU) is characterised by the occurrence of widespread, short-lived weals, appearing daily or almost daily for at least 6 weeks. (1) There has been strong evidence supporting an autoimmune basis of the disease in approximately 27-50% of CU patients, who have functional autoantibodies against the high affinity IgE receptor and/or IgE. (1) A correct diagnosis of autoimmune CU (ACU) is difficult but important because of the presence of more severe clinical symptoms. Currently, autologous serum skin test (ASST) serves as a screening method, after which more adequate confirmation is gained through functional assays, to identify the ACU group.
    British Journal of Dermatology 07/2012; · 3.76 Impact Factor
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    ABSTRACT: Interleukin (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.
    International Archives of Allergy and Immunology 03/2011; 156(1):69-74. · 2.25 Impact Factor
  • Bőrgyógyászati és Venerológiai Szemle. 01/2008; 84(4):120-123.
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    ABSTRACT: 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. 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. 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. 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.
    International Archives of Allergy and Immunology 02/2007; 144(3):217-25. · 2.25 Impact Factor
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    ABSTRACT: Antibodies directed to the alpha subunit of the high affinity IgE receptor and the IgE molecule are proposed to be of pathogenetic relevance in a group of patients with chronic urticaria (CU). The diagnosis of autoimmune chronic urticaria (ACU) is difficult; the autologous serum skin test (ASST) seems to be a useful screening test, but reliable, additional confirmatory methods are needed. To assess the diagnostic value of a modified serum-induced basophil activation test, the CD63 expression assay, in the diagnosis of ACU by comparing the results of the CD63 assay with the results of the histamine release (HR) test, the ASST and serum levels of soluble CD40 ligand (sCD40L). Using basophils from an atopic (DA) and a nonatopic (DNA) donor the activity of sera of 72 patients with CU were measured in HR assay by enzyme-linked immunosorbent assay and in CD63 expression assay by flow cytometry. An ASST was carried out in all patients; in 30 of the 72 patients sCD40L was detected and correlations were derived between the different assays. Sera of 20 normal controls and 26 patients with systemic autoimmune diseases were also tested in the HR assay and in the CD63 expression assay. Histamine-releasing activity was detected in the sera of 51% (DA) and 32% (DNA) of CU patients and 57% (DA) and 28% (DNA) of sera upregulated CD63 expression on the surface of basophils from the different donors. There was a significant correlation between the HR and the CD63 assays carried out on both donors, but the ASST showed a strong correlation with the HR assay only for basophils from the DA. The serum level of sCD40L was significantly higher in patients with CU compared with controls, but the difference between the autoimmune and the nonautoimmune groups was not significant. The CD63 expression assay seems to be a reliable functional test in the diagnosis of ACU, particularly if highly sensitive donor basophils are used, but the determination of the sCD40L serum level was not sufficient to differentiate between the autoimmune and the nonautoimmune patient groups.
    British Journal of Dermatology 08/2006; 155(1):67-75. · 3.76 Impact Factor
  • Börgyógyászati és venerologiaia szemle 01/2006; 82(3):119-125.
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    ABSTRACT: To investigate the intracellular and soluble cytokine levels and T cell subsets in peripheral blood of patients with active and inactive polymyositis and dermatomyositis. The frequencies of T and B lymphocytes, T helper (Th), and T cytotoxic (Tc) cells and of interferon gamma (IFNgamma), interleukin (IL)4, and IL10 expression of CD4+ or CD8+ cells were determined by flow cytometry. The concentrations of soluble cytokines were measured with commercial enzyme linked immunosorbent assays. In active dermatomyositis there was a decreased percentage of T (CD3+) lymphocytes and Tc (CD8+) lymphocytes, decreased IFNgamma expression of CD4+ and CD8+ cells, but an increase in B and IL4 producing CD4+ lymphocyte frequencies. These prominent changes disappeared in the inactive stage of the disease. In polymyositis no significant change in these lymphocyte subsets or in intracellular cytokine expression could be detected in either the active or the inactive form. The frequency of IL4+/IFNgamma+ Th cells was calculated and a significantly increased Th2/Th1 frequency was found in active dermatomyositis, and a decreased frequency in inactive dermatomyositis, compared with the control population. There appears to be a difference between polymyositis and dermatomyositis in the level of peripheral blood lymphocytes and their intracellular cytokine content. These findings provide further evidence for a difference in the pathogenesis of polymyositis and dermatomyositis.
    Annals of the Rheumatic Diseases 11/2005; 64(10):1485-9. · 9.11 Impact Factor
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    ABSTRACT: The autoimmune subclass of chronic idiopathic urticaria (CU) has been characterized by the occurrence of biologically relevant IgG antibodies against the IgE molecule or the alpha chain of the high-affinity Fcepsilon receptor (FcepsilonRIalpha) on basophils and mast cells. These antibodies are usually detected by autologous serum skin testing and confirmed by histamine release studies, immunoblotting, or enzyme-linked immunosorbent assay, but not always. To detect autoantibodies to the FcepsilonRIalpha in sera of CU patients by a modified serum-induced basophil activation test measured by flow cytometry (FCM) and to evaluate the relationship between the in vitro functional test, the autologous serum skin test (ASST), and the serum levels of IgE, eosinophil cationic protein (ECP) and antithyroid antibodies. Sera of 30 patients with CU and 26 patients with systemic autoimmune diseases (systemic lupus erythematosus, dermatomyositis) were tested for CD63 activation marker expression on basophils by FCM. Leucocytes from two highly sensitized atopic donors (D(A1,) D(A2)) and one non-atopic donor (D(NA)) were incubated with patients' sera and double-labelled with anti-IgE and anti-CD63 antibodies. Subsequently, the percentage of CD63-expressing basophils was determined by using FCM. In all CU patients an ASST was carried out and the serum IgE, and ECP levels and antithyroid antibodies were evaluated. Twelve patients had a positive ASST and 14 patients a positive CD63 expression assay. There was a strong correlation between the ASST and CD63 assay. Sera from patients with systemic autoimmune diseases did not raise positive CD63 expression on basophils. There was a moderate negative correlation between the occurrence of atopic serum markers (IgE, ECP) and the ability of sera to induce CD63 expression on basophil cells of D(A2) (P < 0.05). The female sex was preponderant and antithyroid antibodies were more frequent. Our new technical observation demonstrates that basophils of highly sensitized atopic donors can be successfully used without priming with IL-3 for the in-vitro flow cytofluorimetric diagnosis of CU. With this investigation the characterization of the autoimmune origin of CU is based on an objective in vitro technique.
    British Journal of Dermatology 08/2004; 151(2):388-96. · 3.76 Impact Factor
  • Magyar Immunológia. 01/2004; 3(1):46-48.
  • Börgyógyászati és venerologiaia szemle 01/2004; 80(3):133-137.
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    ABSTRACT: 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 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.
    Immunology Letters 05/2003; 86(3):277-80. · 2.34 Impact Factor
  • Börgyógyászati és venerologiaia szemle 01/2003; 79(1):3-7.
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    ABSTRACT: 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 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.
    Immunology Letters. 01/2003;
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    ABSTRACT: 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 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.
    Acta Dermato Venereologica 02/2002; 82(4):249-53. · 3.49 Impact Factor
  • British Journal of Dermatology - BRIT J DERMATOL. 01/2002; 147(6):1135-1141.
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    ABSTRACT: Antibodies produced against the Ro/SSA and La/SSB autoantigens are not only of diagnostic value but they may even play a role in the pathogenesis of several autoimmune diseases (Sjögren's syndrome, subacute cutaneous lupus erythematosus, neonatal lupus erythematosus and systemic lupus erythematosus). Among other factors, ultraviolet (UV) radiation and also the hormonal milieu are well-known cofactors in the pathogenesis of these autoimmune diseases. The goal of our research was to study the possible alterations in mRNA levels of three different Ro antigens and that of two La species produced by alternative splicing in transformed human keratinocytes (HaCaT cells) after UVB irradiation and after 17-beta-estradiol treatment. The polymerase chain reaction technique was used to determine the mRNA levels of the Ro and La species after 24, 48, and 72 h of irradiation. The mRNA levels of calreticulin increased as a function of time after UV irradiation but the mRNA levels of 52 kDa and 60 kDa Ro mRNAs were unaltered. After treating the cells with 17-beta-estradiol, there was no change observed in the levels of Ro mRNAs or La exon 1 mRNA, but a gradual decrease was noted in the mRNA levels of La exon 1'. The importance of alterations in the ratio of La exon 1 to exon 1' is supported by the observations in patients with Sjögren's syndrome, and our results strengthen the notion that the Ro and La antigens participate in the pathogenesis of different autoimmune diseases.
    Archives for Dermatological Research 07/2001; 293(6):275-82. · 2.71 Impact Factor
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    ABSTRACT: 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 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.