Hungarian Immunology

[Biologic therapies in the vasculitides]

SZÁNTÓ Antónia

APRIL 20, 2003

Hungarian Immunology - 2003;2(02)

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Hungarian Immunology

[Immune complex clearance in systemic lupus erythematosus]

KÁVAI Mária, SZEGEDI Gyula

[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

[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

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

KOCSIS Judit, FÜST György, PROHÁSZKA Zoltán

[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

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

POKORNY Gyula, IVÁNYI Béla, SONKODI Sándor, KOVÁCS LÁSZLÓ, KOVÁCS Attila, CSÁTI Sándor, LÁZÁR Máté, MAKULA Éva

[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.]

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Delirium due to the use of topical cyclopentolate hydrochloride

MAHMUT Atum, ERKAN Çelik, GÜRSOY Alagöz

Introduction - Our aim is to present a rare case where a child had delirium manifestation after instillation of cyclopentolate. Case presentation - A 7-year old patient was seen in our outpatient clinic, and cyclopentolate was dropped three times at 10 minutes intervals in both eyes. The patient suddenly developed behavioral disorders along with gait disturbance, and complained of visual hallucinations 20-25 minutes after the last drop. The patient was transferred to intensive care unit and 0.02 mg/kg IV. physostigmine was administered. The patient improved after minutes of onset of physostigmine, and was discharged with total recovery after 30 minutes. Conclusion - Delirium is a rare systemic side effect of cyclopentolate. The specific antidote is physostigmine, which can be used in severely agitated patients who are not responding to other therapies.

Lege Artis Medicinae

[Crucial points in the therapy of hepatitis C]

MAKARA Mihály, HUNYADY Béla

[The first generation of direct acting antivirals represented a milestone in the therapy of hepatitis C but other breakthroughs are on the way with imminent authorization of new antiviral drugs and interferon-free combinations. The prices of these new agents necessitate the rational use of limited financial capacities: relatively cheaper interferon-based treatments could be used first for those who can be cured with these combinations, while the most expensive treatments are to be reserved for those with no other options. In the future, interferonfree regimens will likely be used first in those patients who did not respond to firstgeneration interferon-based regimens and in whom interferon therapy is contraindicated. To avoid complications of the disease, currently it is reasonable to treat all eligible patients with advanced fibrosis, particularly those with compensated cirrhosis, with interferon-based treatments. In some instances other medical or social conditions warrant prompt treatment. The triage of treatments is based on the Priority Index in Hungary. Current triple therapies with protease inhibitors are complicated by drug and food interactions as well as by frequent (sometimes severe) side effects. General practitioners and other specialists need to be involved in managing these issues. It is of utmost importance to refer patients to hepatology care before decompensation or development of hepatocellular carcinoma. The key of timely and accurate diagnosis is organized anti-HCV screening in populations at risk and in the age group with the highest prevalence.]

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[Immune responses and neuroimmune modulation in the pathogenesis of acute ischemic stroke and poststroke infections]

PAPP Viktória, MOLNÁR Tihamér, BÁNÁTI Miklós, ILLÉS Zsolt

[Acute-onset cerebrovascular diseases are connected to a number of immunological changes. Here, we summarize immune responses participating in the evolution of atherosclerotic plaques and poststroke local immune responses in the injured CNS as well as in the systemic circulation. Ischemic injury of the CNS alters the balanced neuroimmune modulation resulting in CIDS, the central nervous system injury-induced immune deficiency syndrome. Due to the immunodepression and reduced pro-inflammatory immune responses, the susceptibility for infection is increased; indeed, poststroke infection plays a major role in stroke-related mortality. On the other hand, CIDS may protect against damaging autoimmune responses elicited by exposed CNS antigens. Investigation of immune responses related to ischemic stroke may result in novel therapies indicated by an increasing number of experimental and clinical trials altering poststroke immune responses and preventing infections.]

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[The relationship of traumatic experiences and eating disorders – therapeutical options]

KOVÁCS-TÓTH Beáta, TÚRY Ferenc

[In the etiology of eating disorders (espe­cially bulimia nervosa and binge eating) traumatic experiences (sexual, physical, emo­tional abuse, neglect) play an important role. Traumatization can have a serious impact, which is influenced by the parameters of the traumatization, risk and protective factors, and the resiliency of the traumatized patient. The consequences may lead to the development of specific psychiatric and somatic disorders, and may cause lifetime revictimization. The exploration of data related to the traumatization is essential in eating disorders as well. If traumatic expericences can be detected in the back­ground of eating disorders, the targeted therapy of eating disorders while applying its specific elements should also follow the guide­lines of the general trauma-therapy. Providing safety in therapeutical relation­ship is fundamental. The therapeutic options are extensive. Along with psychodynamically oriented therapies, the newer methods based on cognitive-behavioral therapy (e.g., dialectic behavior therapy, integrative cognitive analytic therapy) are also proposed. Hyp­no­therapy can also be useful. ]

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[Immunomodulatory treatment in multiple sclerosis ]

CSÉPÁNY Tünde, BERECZKI Dániel

[During the past decade, several disease-modifying agents have been established and have become available for the treatment of multiple sclerosis. The disease-modifying agents could be grouped into immunomodulatory and immunosuppressive therapies altering the long-term course of multiple sclerosis. Therapy is now available for relapsing-remitting, secondary progressive and progressive-relapsing multiple sclerosis. Different disease-modifying agents became also available for the treatment of relapsing-remitting multiple sclerosis in Hungary which makes the therapeutic decision difficult. This overview might help to give an answer for different questions in the management of multiple sclerosis: Which agent to choose? When to initiate the therapy? Which dose to apply? Are the drugs safe? How long to treat the patients with immunomodulatory drugs? We give a review from the literature to assess the efficacy of disease-modifying therapies and to compare the data from phase three trials of interferon β1b, two preparations of interferon β1a or glatiramer acetate for the treatment of multiple sclerosis. We analyzed the efficacy and safety of these agents on physical, inflammatory and cognitive measures of disease activity. Comparison of study results indicated similar effects of immunomodulatory agents on relapse-related and inflammatory measures in relapsing multiple sclerosis. Interferon β1a slowed the progression of disability in relapsing multiple sclerosis. One interferon β1a preparation (intramuscularly injected) demonstrated efficacy in slowing progression of cognitive dysfunction. The interferons reduced relapses at early phase of secondary progressive multiple sclerosis, but their efficacy have not yet been proven in the later phase of secondary progressive multiple sclerosis without relapses. Mitoxantrone demonstrated efficacy in slowing the progression of disability in secondary progressive multiple sclerosis. All of the disease modifying agents are safe and tolerable, if the indication is correct and the patients are strictly controlled.]