Hungarian Immunology

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

VÁRÓCZY László, GERGELY Lajos, ALEKSZA Magdolna, MILTÉNYI Zsófia, ILLÉS Árpád

MAY 10, 2004

Hungarian Immunology - 2004;3(04)

[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.]

COMMENTS

0 comments

Further articles in this publication

Hungarian Immunology

[Therapeutic treatment of rheumatoid arthritis by gene therapy-induced apoptosis]

JAMES M. Woods, VOLIN V. Michael

[Gene therapy was initially conceptualized as a treatment for individuals with genetic disorders, where defective genes would be replaced with functional ones. This concept was eventually broadened to include the use of gene therapy as a delivery mechanism for gene products effective in the treatment of diseases. The latter use of gene therapy, essentially as a drug delivery mechanism, was recognized to be particularly useful in the treatment of rheumatoid arthritis because it may have many advantages over traditional therapies. Two groups of target genes that are potentially useful for gene transfer include soluble inflammatory mediators that in theory could suppress the inflammatory process, and apoptotic mediators that may induce cell death, thereby suppressing the accumulation of inflammatory cells in the joint. To date the former group of target genes has received most of the attention, but it is the latter group of apoptosis-inducing targets that will be discussed in this review. We will focus our discussion on target genes that have shown success at inducing apoptosis in animal models of arthritis and will also include discussion of the apoptotic pathways that are altered in the attempts to reduce inflamed synovial tissue.]

Hungarian Immunology

[History of immunology in Hungary Part V]

KARASSZON Dénes, CSABA Béla

Hungarian Immunology

[Autumn international conferences]

SZEKANECZ Zoltán

Hungarian Immunology

[Immunology of Felty’s syndrome]

BÁLINT Géza, BÁLINT Péter

[Felty’s syndrome can be regarded as “super-rheumatoid” disease. Immungenetically the syndrome is much more homogenous, than rheumatoid arthritis. HLA-DRB1*0401 antigen is present in 83% of the patients. Felty’s syndrome develops usually after a longer course of rheumatoid arthritis, in 1% of rheumatoid patients. Rheumatoid arthritis patients with long lasting unexplained neutropenia can be diagnosed having Felty’s syndrome, even without detectable splenomegaly. On the contrary, rheumatoid arthritis with splenomegaly, but without present or previous neutropenia with unexplained origin cannot be regarded as having Felty’s syndrome. Inspite of the fact, that the arthritis of Felty’s syndrome can be inactive, because of the neutropenia and increased risk of recurrent infections, the patients should be kept under tight supervision, and should be properly treated, if required. Immunologically Felty’s syndrome is characterized by rheumatoid factor positivity in 95-100%, ANA positivity in 50-100%, antihistone positivity in 63-83%. Antibodies against dsDNA rarely, but against ssDNA frequently occur. No anti Sm and interestingly no anti Ro and anti La antibodies can be detected inspite of the high incidence of associated Sjögren’s syndrome. Immunoglobulin levels are higher and complement levels are lower, than in rheumatoid arthritis. Circulating immuncomplex level is usually high. Non-specific antineutrophil anticitoplasmatic antibodies can be found in high percentage. The neutropenia of Felty’s syndrome can be either caused by increased IgG neutrophilic binding activity or by inhibition of the granulocytes colony growing in the bone marrow, by peripheral blood mononuclear cells. Expansion of large granular lymphocytes can be seen in 30-40% of patients with Felty’s syndrome. Large granular lymphocyte syndrome is not rarely associated with rheumatoid arthritis. The neutrophil account is normal or elevated in this syndrome, but splenomegaly occurs. These cases are called as pseudo Felty’s syndrome. The patients with Felty's syndrome suffering from recurrent infections required treatment even if the arthritis is inactive. Methotrexate treatment should be started first, if this treatment fails, other disease modifying drugs or colony stimulating factor can be given. There is no experience with other biological treatments. In treatment of resistant cases splenectomy is indicated. Non-steroid anti-inflammatory drugs should be better avoided.]

Hungarian Immunology

[Changes of immune system in the elderly]

MEKKEL Gabriella, BARTA Zsolt, BAKÓ Gyula

[”Immunosenescence” means the change of the immune system with ageing. Ageing of the immun system is a physiological process, based on complex immunregulatory alterations, which make the elderly more susceptible for infections, malignant and autoimmun diseases. It’s important to differentiate the primary (physiological) and secondory (caused by diseases) modifications of immunregulatory system. After reviewing the strict Senieur protocoll, which makes a basis for gerontological/geriatry studies, the authors survey in details the changes of the each cell types of the immune system. The impaired functions of the NK (natural killer) and PMN (polymorphonuclear) cells and macrophags (as the parts of innate immunity), the decreased numbers of T lymphocyts, and the less specific antibodies produced by B lymphocyts (as the part of the acquired immunity) together are responsible for the increased susceptibility of the elderly to infections, and for the higher prevalence of malignancies in elderly patients. The imbalance of pro- and anti-inflammatoric cytokines and the TH1- TH2 shift also play role in this process. Appearance of autoantigens and the increased autoreactivity are in the background of the frequency autoimmun diseases in the elderly. The development of malignant diseases is a complex process, caused by on the one hand the changes in innate immunity, on the other the decreased activity of suppressor mechanisms. These changes are not correctly known, but the literature grows increasingly. The good command of the molecular mechanisms provides the facilities to improve remedial interventions in the future.]

All articles in the issue

Related contents

Lege Artis Medicinae

[LATE COMPLICATION OF EXTRANODAL LYMPHOMA FOLLOWING DERMATOMYOSITIS]

VÁNCSA Andrea, PONYI Andrea, CONSTANTIN Tamás, GERGELY Lajos, DANKÓ Katalin

[INTRODUCTION - Intramuscular follicular Bcell lymphoma is a rare entity of malignant lymphomas complicating the disease course of dermato/polymyositis. CASE REPORT - The authors report a female patient who was diagnosed with dermatomyositis in 1963 (age of 36). She was given steroid and hydroxychloroquine therapy. In 1973 she was treated with steroid for Boeck sarcoidosis. In 1999, she was treated for steroid therapy again for reoccurence of dermatomyositis. In 2000, a histological diagnosis of primary intramuscular follicular lymphoma was established from the right thigh region. She was given several courses of polychemotherapy and radiation therapy, but the lymphoma was difficult to control, and she died of progressive disease in 2003. CONCLUSION - It is an interesting case as 37 years elapsed since the diagnosis of dermatomyositis before the lymphoma has started. We could not state a definite relation between the myositis and the lymphoma but the increased frequency of autoimmune diseases is probably due to immune regulatory problems, that have eventually led to the appearance of the rapidly growing indolent lymphoma.]

Hungarian Immunology

[Extensive flow cytometric characterization of plasmocytoid dendritic cell leukemia cells]

GOPCSA László, KORMOS Luca, BÁNYAI Anikó, TAMÁSKA Júlia, MATOLCSY András, GOGOLÁK Péter, RAJNAVÖLGYI Éva, PÁLÓCZI Katalin

[INTRODUCTION - Accumulating evidences suggest that non-T, non-B cell CD4+/CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. CASE REPORT - In this work we present the immunophenotypic and genotypic features of bone marrow, peripheral blood, lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, bone marrow, peripheral blood, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation and co-stimulatory molecules were used. The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2 and granzyme-B corresponding to the preplasmacitoid dendritic cell developmental stage. CONCLUSION - The presence of CD11a/CD18, CD84, CD91, CD95, αvβ5, CDw197 and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells.]

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. Mátyás, SCHWEITZER Katalin

[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.]

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

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

PÁLÓCZI Katalin, NÉMETH Julianna, BÁNYAI Anikó, GOPCSA László

[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.]