Hungarian Immunology

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


APRIL 20, 2003

Hungarian Immunology - 2003;2(02)

[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.]



Further articles in this publication

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.]

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.]

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

[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

[Biologic therapies in the vasculitides]

SZÁNTÓ Antónia

All articles in the issue

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Hypertension and nephrology

[Recent developments in the diagnosis and therapy of haemolytic uremic syndrome. Part 1: Diagnosis and initial therapy]

PROHÁSZKA Zoltán, SZILÁGYI Ágnes, SZABÓ Melinda Zsuzsanna oh., RÉTI Marienn, REUSZ György

[In this summary an overview is offered on the recent developments of the investigation and the treatment of hemolytic uremic syndrome. Based on the recent developments in the understanding of the pathogenesis and on the novel diagnostics there is an increasing ability to identify the etiology of specific diagnostic sub-groups of the disease. This molecular etiology-based classification and sub-group diagnosis has substantial influence on the short-term and long-term management of the affected patients. The first part of our review focuses on the steps of first and second line diagnosis and the selection between available therapeutic options, and provides flow-charts for the daily work. The various aspects of the long-term management and disease monitoring in hemolytic uremic syndrome will be reviewed in a second article in the future.]

Lege Artis Medicinae



[In this review we summarise the current results of the genomic investigation of allergic diseases. From the genetic point of view allergy is multifactorial, which means that the susceptibility to the disease is determined by the effect of one or more genes or the interactions between multiple genes and involves important nongenetic factors such as the environment for their expression. Among allergic diseases the genomic background of asthma was studied most thoroughly. Until now, using hundreds of DNA markers, located across all of the human chromosomes, 16 genome-wide screens for susceptibility genes for asthma or asthma related intermediate phenotypes in 12 different populations have been published and 20 chromosomal regions have been highlighted for further analysis. In genetic association studies more than 500 genes were identified as candidate genes for asthma. In this review, we selected those results which were consistently reported by several independent studies or appeared particularly important or interesting. According to the results of the human genome programs and association studies we discuss the possible roles of candidate genes found in these loci in the pathomechanism of allergy and atopy.]

Clinical Neuroscience

[Serum IgG and IgM ganglioside GM1 antibodies in patients with multiple sclerosis]

ZAPRIANOVA Emilia, MAJTÉNYI Katalin, DENISLAVA Deleva, OLIA Mikova, ANDON Filchev, BORISLAV Sultanov, VERA Kolyovska, SULTANOV Emil, LILIA Christova, XENIA Kmetska, DIMITAR Georgiev

[INTRODUCTION - In order to obtain more information concerning the pathogenic significance of ganglioside GM1 in multiple sclerosis serum polyclonal IgG and IgM antibodies to GM1 were evaluated in multiple sclerosis patients with relapsing-remitting and secondary progressive forms of the disease. PATIENTS AND METHODS - The evaluated sera were from 55 patients with clinically definite multiple sclerosis and from 20 healthy subjects. Forty-two of patients were with relap-sing-remitting and 13 with secondary progressive multiple sclerosis. Antibodies to GM1 were measured using a modification of the enzyme-linked immunosorbent assay technique of Mizutamari et al (1994). RESULTS - A statistically significant difference of serum IgG antibody titres to GM1 was found between the healthy subjects and the multiple sclerosis patients with relapsing-remitting form of the disease (p=0.04), as well as of serum IgG antibody titres to GM1 between the patients with relapsing-remitting multiple sclerosis in relapse and in remission (p=0.01). CONCLUSION - Bearing in mind the heterogeneity of multiple sclerosis, the pathogenic significance of serum antibo-dies to GM1 should be interpreted concerning the precise clinical form of the disease and not the whole group of MS patients. The findings in this study argue for the possible involvement of ganglioside GM1 in the pathogenesis of demyelination in relapsingremitting multiple sclerosis.]

Hypertension and nephrology

[Association between the genetic polymorphism of heat-shock protein 72 and pediatric kidney diseases]

BÁNKI Nóra Fanni, RUSAI Krisztina, KÁROLY Éva, SZEBENI Bea, VANNAY Ádám, SALLAY Péter, REUSZ György, TULASSAY Tivadar, SZABÓ J. Attila, FEKETE Andrea

[Recurring urinary tract infections (UTI) in childhood may result in chronic- and end-stage-renal-disease (ESRD), which leads to the initiation of dialysis and renal transplantation (NTx). Heat shock protein (HSP) 72 protects the kidney, whereas it refolds destroyed proteins and cells, and helps regenerating the renal tissue. The HSPA1B (1267)G allele is associated with lower HSP72 expression. This study assesses the role of HSPA1B A(1267)G polymorphism using PCR-RFLP in 103 children treated because of recurrent UTI, 26 children after NTx and 235 healthy controls. Clinical data were also evaluated. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele occurred more frequently in the UTI (p=0.0001; CI: 1.378-2.68) and in the NTx (p=0.014; CI: 2.29-187.7) patient group than in the controls group, and were associated with a higher risk for scarring (p=0.012; CI: 0.33-1.00) and renal malformation (p=0.0072; CI: 1.623- 140.6). Our data indicate a relationship between the carrier status of HSPA1B (1267)G allele and the development of recurrent UTI and ESRD, raising further questions about the clinical and therapeutic relevance of these polymorphism.]

Clinical Neuroscience

[Investigation of insertion/deletion polymorphism of the ACE gene on stroke patients]


[Introduction - This is the first Hungarian paper on the insertion/deletion polymorphism of ACE gene in stroke patients. According to literature data, the role of this polymorphism is controversial in the pathogenesis of stroke. The aim was to study the prevalence of the polymorphism in healthy persons and in stroke patients. Patients and methods - Blood samples from 173 unrelated healthy donors and 253 stroke patients were investigated by polymerase chain reaction (PCR). Preivous stroke was documented by CT or MRI and CDS. A routine questionnaire was used to study previous vascular events and the risk profile of patients. Results - I/I allele was found in 20%, I/D 52% and D/D 28% in the healthy group. Prevalence of the pathologic D/D allele did not differ between healthy and patients group (28% and 27%, OR: 0.88, and in subgroup age under 50 years OR: 1.00). No correlation was found between D/D and conventional risk profile but a positiv correlation was found in young patients having D/D and hyperlipidemia (p<0.05) and hyperfibrinogenemia (p<0.05). D/D prevalence was found higher in patients with family anamnesis of myocardial infarction (p<0.05). Very low prevalence of D/D allele was found in cardiogen embolic group (p>0.05). Conclusions - The ACE polymorphism does not seem to be an independent risk factor for stroke. However, in young stroke patients with D/D allele, hyperlipidemia and/or hyperfibrinogenemia present very high risk for stroke.]