Lege Artis Medicinae

[A novel rapid IL-6 release assay using blood mononuclear cells of patients with various forms of drug induced skin injuries]

BALÓ-BANGA J. Mátyás1, SCHWEITZER Katalin2

SEPTEMBER 22, 2013

Lege Artis Medicinae - 2013;23(09)

[INTRODUCTION - IL-6 is a multifunctional cytokine with effects on the haematopoiesis on differentiation of T and B lymphocytes and on the regulation of both inflammatory and allergic reactions. The question arose whether this substance excreted by mononuclear cells could be used as a marker of allergy to drugs or not. Till now equivocal descriptions were lacking. METHOD - The preformed IL-6 present in the mononuclear cells released by any of four standard dilutions of pure substances upon 20 minutes incubation was determined from the supernatants by ELISA technique. In vivo patch, intradermal and provocation tests were carried out along with this assay (483 in vitro and 172 in vivo). RESULTS - Two different groups suspect for drug allergy (100 and 62 patients as well as their matching controls, 24 and 23 persons) were involved with these procedures. In some cases TNF-α, IL-2, IFN-γ and IL-4 was measured simultaneously by flow cytometric assay. Only TNF-α and IL-6 were present in the 20 min. supernatants. The comparisons with in vivo tests have confirmed that the amount of IL-6 release had not depended either on the clinical phenotype of allergy or on the structure of the tested drugs within the molecular mass range between 76-4000 Da. IL-6 released at the lowest or multiple concentrations of drugs coincided with more severe and widespread clinical forms. CONCLUSION - Based on the results we elaborated an in vitro method applicable clinically for detecting drug sensitisation and its differential diagnosis in patients with skin signs of drug sensitisation.]

AFFILIATIONS

  1. Magyar Honvédség, Honvédkórház, Bôrgyógyászati Osztály és Szakambulancia
  2. Magyar Honvédség, Honvédkórház, Kórélettani és Immunológiai Laboratórium

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[Drug use and death-seeking behaviour attitudes toward death among opiate users]

PAP Ágota, HEGEDÛS Katalin

[Many times, behind mens’ fears there is the fear of death. Drug use can be defined as a kid of self destruction, so it is directly linked to attitudes toward death. In Hungary, suicide among young people is one of the leading causes of death, which is often associated with some kind of addiction or substance abuse. We can also say that drug use is an indirect way of “death search”, which prolongs the agony and the time of suffering. Drug-related death can be directly attributed to drug overdose. Intravenous drug use may cause a risk of infectious diseases (such as sharing needles/syringe/filter use) - HCV, AIDS, etc. Intravenous drug use is mostly - but not exclusively - characteristic to opiate users. Heroin’s mode of action is described as causing an intense feeling of euphoria and a way of feeling augmenting to stupor. Its addictive potential is very high, the degradation is visible and can be fatal. In this paper, we discuss previous observations on overdose that is the validity of harm reduction justified by former research, the possible predictors of overdose and the identification of the prevention area.]

Lege Artis Medicinae

[Changes to the Mind ]

TAKÁCS Szilvia

Lege Artis Medicinae

[Treatment of patients with hepatitis C infection (genotype 1), severe fibrosis or compensated cirrhosis: telaprevir early access program in Hungary]

TORNAI István, HORVÁTH Gábor, GERVAIN Judit, MAKARA Mihály, BÁNYAI Tivadar, VINCZE Áron, SZALAY Ferenc, LONJON-DOMANEC Isabelle, HILL Andrew, HUNYADY Béla

Lege Artis Medicinae

[Letrozol therapy of postmenopausal women with early-stage breast carcinoma after four-six years of tamoxifen therapy: tolerability and quality of life]

TÓTH Éva Katalin, NEMESKÉRI Csaba, SZABÓ Barna, URBANCSEK Hilda, MÉSZÁROS Edina, NAGYKÁLNAI Tamás, PESTI Lajos, MARKÓ László, NAGY Beatrix, LANDHERR László

[INTRODUCTION - In patients with hormone- dependent breast cancer, five-year postoperative tamoxifen therapy is a standard treatment approach. Continuing this therapy for more than five years can increase the risk of recurrence of the disease. It has been shown that treatment with the third-generation aromatase inhibitor letrozol after discontinuation of tamoxifen therapy significantly improves disease-free survival. It is important to assess whether the substantial decrease of estrogen level shows a correlation with the occurrence of unwanted events/side effects or with changes in the quality of life. PATIENTS AND METHOD - Between 2005 and 2009, 921 women (mean age 63 years, age 40-94 years) with early-stage breast carcinoma were treated with expanded adjuvant letrozol therapy following tamoxifen treatment. Of these patients, 541 received previous tamoxifen therapy for 4-6 years. We studied relapses and quality of life - measured by the SF-36 survey - during letrozol therapy in the latter patient group and the occurrence of unwanted events and side effects in all 921 patients. The patients were examined eight times and completed the survey four times. RESULTS - At the check-ups, relapses were recorded in case of 20 patients. Quality of life scores significantly increased in two main categories - physical and mental health -, and within these in three subcategories, whereas decreasing scores were not recorded in any categories. In 921 patient taking letrozol, 73 experienced unwanted events/side effects, of which nine were severe and three patient died. The two most common side effects were joint and bone pain (18 patients) and heat rash (12 patients). CONCLUSION - Extended adjuvant therapy with letrozol efficiently decreased the number of relapses and the number of patients continuing therapy. On the basis of the SF-36 survey the patients’ quality of life generaly improved. Letrozol therapy was well tolerated by most patients, which can have a favourable effect on the outcome of the therapy.]

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GERLINGER Imre

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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

[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

[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.]

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.]

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

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[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.]