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

[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

[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]

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.]

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.]

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Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study

NÉMETH Klára Zsófia, SZÛCS Anna , VITRAI József , JUHÁSZ Dóra , NÉMETH Pál János , HOLLÓ András

We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05–1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27–3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16–0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

Clinical Neuroscience

[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]

BOCZÁN Judit, KLIVÉNYI Péter, KÁLMÁN Bernadette, SZÉLL Márta, KARCAGI Veronika, ZÁDORI Dénes, MOLNÁR Mária Judit

[Background – Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose – The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods – Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients – We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.]

Clinical Neuroscience

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.

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[Practical aspects of anticoagulant treatment during the COVID-19 pandemic]

KOMÓCSI András

[Coronavirus infection has a multiple im­pact on the coagulation system and anti­coagulant therapies. Patients admitted with COVID-19 have un­usually high incidence of coagulation ab­normalities. The incidence of atrial fibrillation (AF) seems also to be more frequent among COVID-19 out- and especially in-patients. Among COVID-19 patients receiving oral anticoagulant therapy, for minimizing the risk of bleeding or thromboembolic complications there should also be considered the renal and hepatic functions and drug-drug interactions of oral anticoagulant and COVID-19 therapy. In case of direct anticoagulants, in addition to the benefits of better safety, more favorable treatment ad­he­rence, and fixed dosing, the use of this class of drugs does not require laboratory mo­nitoring of efficacy, which may be of exp­licit benefit in terms of social distancing and health network burdens. This study reviews the possible interactions of drugs used for viral infection and anticoagulation, and in addition to the issues of coagulopathy associated with COVID-19, we discuss also the concerning difficulties of continued anticoagulant therapy related to the social distancing measures.]

Clinical Neuroscience

[Pharmacological and nonpharmacological treatment of insomnias with regard to sleep medicine]

FALUDI Béla, ROZGONYI Renáta

[Insomnia - one of the most prevalent sleep complain - has a great impact on the everyday life. Basically two different form of insomnia can be defined: the insomnia disorder and the co-morbid insomnias. To treat adequately determination of background pathology is essential, which is based on the help of Sleep Medicine Centers. According to the newest guidelines, the treatment of insomnia disorder is based on cognitive behavioural therapies followed by pharmaceutical intervention. In this review we provide the short description of cognitive behavioural therapies and basic principles of hypnotic drugs. Despite the availability of insomnia guidelines the huge variation of the insomnia medication can be seen in the daily practice. Due to the above mentioned reasons we summarize the good clinical practice of hypnotic drug administration for insomnia patients.]