Hungarian Immunology

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

PÁLÓCZI Katalin, NÉMETH Julianna, BÁNYAI Anikó, GOPCSA László

APRIL 20, 2003

Hungarian Immunology - 2003;2(02)

[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.]



Further articles in this publication

Hungarian Immunology

[The outcome of the renal involvement in primary Sjögren’s syndrome]


[OBJECTIVE - Kidney function re-evaluation in primary Sjögren’s syndrome (P-SS) patients years after the first signs of renal involvement. PATIENTS - Of 75 primary SS patients followed up for various periods between 1990 and 1999, 11 had overt kidney involvement. The mean age of these 11 at the time of diagnosis of renal manifestations (first examination) was 39.6 years. In nine of the 11, the renal function was re-examined (second examination: NH4CL loading, determination of urinary concentrating ability, proteinuria and technetium99m-mercaptoacetyltriglycine clearance) on average 8.8 years later. RESULTS - At the first examination overt renal tubular acidosis (RTA) was diagnosed in 11 patients (proximal in one and distal in 10), accompanied by hyposthenuria in five, and proteinuria >0.5 g/24 h in four. Tubulointerstitial nephritis (TIN) was diagnosed in all four biopsied patients with proteinuria, and cryoglobulinaemic glomerulonephritis in one of them. Seven of the 11 were treated with moderate or low doses of glucocorticosteroids, and two with repeated methylprednisolone pulse therapy. The acidification capacity of the kidneys and degree of proteinuria mostly improved significantly (p<0.001), but the degree of hyposthenuria did not change essentially between the examinations. CONCLUSIONS - The outcome of the kidney manifesztation in primary Sjögren’s syndrome is usually favourable, but end-stage renal failure can develop rarely.]

Hungarian Immunology

[Biologic therapies in the vasculitides]

SZÁNTÓ Antónia

Hungarian Immunology

[Molecular biology of 70 kD heat shock protein and its role in certain immunological processes]


[Heat-shock proteins, or stress proteins play important role in cellular survival owning to their protective function. Their highly conserved structure renders them ideal messengers of cellular stress response. One of the best known representative of these proteins is the 70 kDa heat-shock protein (Hsp70), there is increasing amount of data about the intraand extracellular functions of this stress protein. In the present review the regulation of hsp70 gene expression, and hsp70 polimorfisms, the possible impact of polymorphisms to certain diseases, and the multilevel relationship between Hsp70 and the immun response are discussed. The authors review the role of Hsp70 in anti-tumor immunity, and the presence of anti-Hsp70 antibodies and their possible association with certain diseases. Here they present some of their recent observations: they detected the presence of anti-Hsp70 antibodies in all adult sera and found no correlation between these antibody levels and the presence of severe coronary heart disease. Recently we also showed, that human Hsp70 can activate the classical pathway of complement system in vitro, by direct binding of the first complement C1q.]

Hungarian Immunology

[Autoantibodies against α-fodrin in patients with Sjögrens’s syndrome]

SZÁNTÓ Antónia, CSÍPŐ István, ZEHER Margit

[INTRODUCTION, PATIENTS AND METHODS - In this study, the authors examined the presence of the IgA and IgG type autoantibodies against the 120 kDa α-fodrin in the sera of patients affected with primary and secondary Sjögren’s syndrome, rheumatoid arthritis and systemic lupus erythematosus, being treated in the Department of Clinical Immunology of the 3rd Department of Internal Medicine, at the University of Debrecen. As a control population, the sera of healthy blood donors were used. RESULTS - Due to their findings, the presence of autoantibodies against the α-fodrin was significantly higher in patients with primary Sjögren’s syndrome than in the control group. The presence of these autoantibodies occurred significantly more often in patients affected with secondary Sjögren’s syndrome associated to RA and SLE, than in these polysystemic autoimmune diseases without sicca-syndrome. Interestingly, they couldn’t find any connection between the presence of autoantibodies against α-fodrin and the occurrence of SS-A/Ro or SS-B/La autoantibodies. There was no correlation in primary and secondary Sjögren’s-syndrome between the extraglandular symptomes or the swelling of the salivary glands and the presence of the anti-α-fodrin autoantibodies. CONCLUSIONS - The autoantibodies against α- fodrin might be important in the diagnosis of the juvenile Sjögren’s syndrome and other juvenile autoimmune diseases, in the early diagnose of Sjögren’s syndrome, especially in the lack of anti-SSA/ Ro and anti-SS-B/La.]

Hungarian Immunology

[Immune complex clearance in systemic lupus erythematosus]


[Impaired clearance of immune complexes is regarded as a central factor in the pathogenesis of systemic lupus erythematosus (SLE). Receptors for IgG (FcγRs) are expressed on phagocytes and madiate binding and endocytosis of IgG immune complexes. At first the binding of the ligand to the receptor of monocytes was determied with reaction kinetic method and microscopically. The results demonstrated that the binding of monomeric IgG is higher but that of immune complexes is lower to receptors of patient's monocytes. This discrepancy could be explained than the molecular heterogeneity of FcγRs on human phagocytes was revealed. The FcγRI binds the monomeric IgG, at the same time the FcγRII and III both bind and ingest the immune complex. After that the expressions of the different FcRs, as antigens, were investigated with monoclonal antibodies in flow cytometer. According to the authors' earlier results the expression of FcγRI on monocytes of patients was elevated but that of FcγRII and III were decreased parallely with the phagocytosis. The explanation for this discrepancy may be the structural and functional difference of the FcγR. The expressions of FcγRII and III decreased also on the granulocytes of patients. Impaired in vivo clearance of particle immune complex was measured in SLE patients correlated with the clinical activity of disease and the renal involvement. The data suggest that the alterations of FcγRI expression on phagocytes in SLE are much better a disease-related process and depend on acquired factors than on inherited one. In the transport of complement containing immune complex to macrophages the erythrocyte complement receptors (CR1) has important activity which are also decreased in SLE. The number of CR1 on erythrocytes was investigated by the binding of labelled ligand and monoclonal antibodies to the receptor in flow cytometer in paralell with the genetically determination of receptor expression. The data revealed a correlation between kidney involement of patient and CD1 deficiency, and their expression can be corrected with epoetin α treatment and with plasmapheresis. These data also suggest the role of acquired factors contributing to CR1 deficiency in SLE.]

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Lege Artis Medicinae


BENE Ibolya, ERŐS Nóra, KÁROLYI Zsuzsánna, TAKÁCS István, RADVÁNYI Gáspár

[INTRODUCTION - Haematologic malignancies can originate from the skin (cutaneous lymphomas, rarely acute myelomonocytic leukemia) or can infiltrate the skin secondarily during the progression of the disease (nodal and systemic non-Hodgkin’s lymphomas, Hodgkin'’s disease, chronic lymphocytic leukemia). PATIENTS AND METHODS - The clinical history of seven patients treated by the authors between 1997-2003, is reviewed. CONCLUSIONS - The clinical and histopathologic features of each entity are discussed, emphasizing differences in the clinical course between cutaneous and nodal lymphomas, considering diagnostic difficulties, conventional and recent therapeutic approaches.]


[Femoral head osteonecrosis in a child with acute lypmhoblastic leukemia]


[INTRODUCTION - The treatment of pediatric leukemia has become increasingly successful, with a survival rate over 80%. Thus interest has been increasingly focused on the long-term side-effects of the treatment. The questions of reduced fertility rate, occurance of second malignancies, cardiomyopathy, impaired renal and pulmonal function have been extensively studied. Changes of bone metabolism in connection with the disease itself and the treatment have been analysed in the past decade. CASE REPORT - We present the case of a 15-year-old boy with acute lymphoblastic leukemia, who had bone pain soon after the diagnosis. During the course of chemotherapy his complaints were fluctuating, and he developed severe osteoporosis. The level of a bone resorption marker, β-CrossLaps, was elevated. In the second year of therapy an acute pain of the left hip occured with fever and restriction of joint movement, which was diagnosed and treated as osteomyelitis. A few months later avascular necrosis of the left femoral head was revealed. Both pharmaceutic (calcium, vitamin D, calcitonin, bisphophonate) and orthopedic treatment were used, as a result bone mineral density and movement restriction improved; his leukemia is now in remission. CONCLUSIONS - The factors influencing bone metabolism in leukemic children are reviewed. Firstly the effects of malignant cells on bone mineral content are analyzed, then the chemotherapeutic drugs’ mechanisms of action are examined extensively. The direct and indirect effects of secondary factors (hospitalization, immobility, lack of sun exposure, malabsorption, immunsuppression, peripheral neuropahty) are also analyzed. The advantages and disadvantages of drugs used in preventing and treating childhood osteopenia are reviewed.]

Hungarian Immunology

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


[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.]

Lege Artis Medicinae



[INTRODUCTION - Diffuse large B-cell lymphoma frequently has bone involvement, but primary bone lymphoma is rare (around 4% of primary extranodal lymphomas). Long bones are most often affected, followed in frequency by the ribs, vertebrae, and pelvic bones. The main symptom is bone pain. CASE REPORT - The case of a young man is presented whose disease started with lumboischialgia. Since rheumatological treatment did not relieve the symptoms, MRI was performed, which showed a tumour with massive iliac bone destruction. Three months after the initial symptoms a surgical biopsy from the right ilium showed diffuse large B-cell lymphoma. Soon after acute renal insufficiency developed and the patient was put on haemodialysis. Based on the findings the disease was staged as Ann Arbor IV/B (bone and kidney), ECOG PS 3, International Prognostic Index 4. On the basis of the preliminary histological findings, reduced-dose CHOP chemotherapy was given, which resulted in a significant improvement of the renal function and haemodialysis could be abandoned. This was followed by 6 additional cycles of Rituximab-CHOP treatment and further 2 cycles of Rituximab-DHAP salvage chemotherapy with intrathecal prophylaxis, and, finally, since no response could be detected, R-IVAC treatment was given. After an initial response, the disease became progressive, and the patient died 9 months after the diagnosis was made from a disseminated chemoresistant disease. Autopsy confirmed extensive infiltration of the right iliac bone, kidneys, bone marrow, spleen, supraclavicular and abdominal lymph nodes, pancreas, scalp and brain. CONCLUSIONS - This case was chosen to be presented because of the unusual localisation of the diffuse large B-cell lymphoma, the initial diagnostic difficulty, and the very rapid progression despite the application of several aggressive chemotherapy schemes. A primary bone large B-cell lymphoma represents a diagnostic challenge with its rheumatological symptoms thus delaying diagnosis.]

Lege Artis Medicinae

[New molecular based methods for diagnosis, classification and prognosis of leukemias]

ZVARA Ágnes, HACKLER László, PUSKÁS László G.

[Normal functions of the cell are based on the precise regulation of various genes. If this strict regulation and the hierarchy of genes becomes upset due to some flaws of the system, the result will be cellular dysfunction which may eventually lead to carcinogenic transformation. The two main challenges in the classification of cancers are the discovery of new molecular markers characteristic to defined disease groups and the classification of already diagnosed or new cases into existing groups. This precise classification may open the door to tailored treatment or project the expected outcome of the disease. Today, there is unlimited access available to the databases containing sequences and localisation of the genes within the confines of Human Genome project. It provides significant help for the discovery of chromosome abnormalities and systematic analysis of gene expression patterns. This is important not only to understand normal functions of the cells, but it also contributes to the identification of new genes that are characteristic to given disease groups as markers and that are potential drug targets. Until the second half of the twentieth century the study of the function and regulation of genes was based on step by step investigation of individual genes. The fact that the genomes of an increasing number of organisms have become identified in whole or in part, numerous new techniques have been developed facilitating the systematic analysis of gene functions. The aim of this study is to summarise the new, molecular based possibilities for classification, diagnosis and prognosis of cancers, as well as to summarise the results of these areas, primarily from the point of view of leukemias.]