Beatrix Irinyi

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

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-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 + /IFN-γ + lymphocytes (30.3±8.8%) while the percent of CD4 + /IL-4 + cells (0.37±0.31%) were significantly ( P + /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 H 1/T H 2 balance in psoriasis measured in non-separated whole blood T cells.

Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitis.

Summary Background  A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon‐γ (IFN‐γ) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD).

Basophil CD63 expression assay on highly sensitized atopic donor leucocytes—a useful method in chronic autoimmune urticaria

Background  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 α chain of the high‐affinity Fcɛ receptor (FcɛRIα) 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.

Significant correlation between the CD63 assay and the histamine release assay in chronic urticaria

Background  Antibodies directed to the α 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.

Altered cytokine expression of peripheral blood lymphocytes in polymyositis and dermatomyositis

Objective: To investigate the intracellular and soluble cytokine levels and T cell subsets in peripheral blood of patients with active and inactive polymyositis and dermatomyositis. Methods: The frequencies of T and B lymphocytes, T helper (Th), and T cytotoxic (Tc) cells and of interferon γ (IFNγ), 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. Results: In active dermatomyositis there was a decreased percentage of T (CD3+) lymphocytes and Tc (CD8+) lymphocytes, decreased IFNγ 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+/IFNγ+ 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. Conclusions: 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.

Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis

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.

Clinical and Laboratory Examinations in the Subgroups of Chronic Urticaria

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% 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.

Cytokine Production of CD4+ and CD8+ Peripheral T Lymphocytes in Patients with Chronic Idiopathic Urticaria

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.

Regulatory T-cell subsets with acquired functional impairment: important indicators of disease severity in atopic dermatitis.

Our aim was to assess whether the presence of highly active effector T cells in atopic dermatitis (AD) is associated with changes in the number and/or function of regulatory T cells (Tregs). Flow cytometry was utilised to determine the percentage of CD4+ CD25bright CD127-/low FOXP3+ and skin-homing CLA+ CD4+ CD25bright FOXP3+ Tregs in healthy controls and AD patients. The correlation between disease severity and Treg percentages was estimated. Treg suppressor activity and cell proliferation were measured after T-cell stimulation. Significantly increased percentages of Tregs were found in AD patients compared to healthy individuals, and significant correlation between the frequency of Tregs and disease severity was also detected. The otherwise normal suppressor activity of Tregs decreased in the presence of Staphylococcus enterotoxin B (SEB). In conclusion, the continuous presence of SEB can trigger an acquired functional impairment of Tregs in AD patients and the correlation between the increased frequency of Tregs and disease severity supports their important role in AD pathogenesis.

Extended diagnostic value of autologous serum skin test and basophil CD63 expression assay in chronic urticaria

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