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Lege Artis Medicinae

OCTOBER 20, 2018

[Gene modified T cells against cancer]


[Chimeric antigen receptor modified (CAR) T cells are hailed as a revolutionary breakthrough in the field of oncology. CAR T cells were first applied, with outstanding success, in the treatment of various leukaemias, yielding unprecedented antitumor activity and long periods of disease free survival. Following the success of CAR T cell therapy in leukaemias, solid tumors should now be targeted. These are more complex targets, therefore CAR T cell therapy needs to be further optimized for this purpose. Also, some unfortunate side effects, including the potentially deadly global inflammation called cytokine storm have to be minimized and possibly even eradicated. The next decade will be an exciting time to define whether this therapy which is yet exclusively used for cancer patients is also successful in the treatment of other diseases. In a recent study, T cells reengineered with CAR derived chimeric autoantibody receptors (CAAR) efficiently prevented disease progression in pre-clinical animal models simulating the serious autoimmune disorder, pemphigus vulgaris. Therapy was based on CAAR constructs which have the unique ability to selectively recognize and eliminate the B-cell clones secreting autoantibodies against a self-protein, thus playing a key role in disease pathogenesis and progression. In this review, we would like to give an overview about the history of the CAR T-cell concept, summarize briefly the currently running clinical trials, and discuss the challenges and future prospects of CAR T-cell therapy.]

Hypertension and nephrology

DECEMBER 20, 2016

[New development in the pathogenesis, diagnosis and treatment of IgA nephropathy]

NAGY Judit, VAS Tibor, KOVÁCS Tibor

[IgA nephropathy is one of the leading cause of primary glomerulonephritis worldwide. IgA nephropathy is regarded as an immune mediated disease with a multi-hit pathogenesis starting with the production of poorly glycosylated IgA1 and glycan-specific IgG and IgA autoantibodies leading to the formation of IgA1 containing immune complexes. These immune complexes deposit in the glomerular mesangium followed by the onset of mesangioproliferative glomerulonephritis. The disease has variable clinical presentation and outcome. There is a need to identify patients who have the potential to progress to end-stage renal disease with the help of clinical, histological and biological markers. Treatment options for IgA nephropathy are largely based on opinion or weak evidence. It is true for the KDIGO Clinical Practice Guideline for Glomerulonephritis treatment recommendations containing low level of evidence for almost all recommendations related to IgA nephropathy. It is suggested to separate the patients into 3 groups on the basis of risk to progression and to give not-specific supportive treatment (especially angiotensin converting enzyme inhibitors or angiotensin receptor blocking agents) to all of them on the basis of the risk factors. We discuss the recommendations of the KDIGO Guideline about steroid and immunosuppressive treatment for moderate and high risk patients. Lastly, we provide our perspective on the existing other treatment options (tonsillectomy etc.) and on ongoing clinical trials.]

Clinical Neuroscience

SEPTEMBER 30, 2014

[Anti-signal recognition particle autoantibody positive myopathy]

BODOKI Levente, VINCZE Melinda, HORTOBÁGYI Tibor, GRIGER Zoltán, CSONKA Tamás, DANKÓ Katalin

[The idiopathic inflammatory myopathies are systemic, autoimmune diseases characterized by proximal symmetrical muscle weakness. We review the myositis-associated and myositis-specific autoantibodies, among them the anti- SRP autoantibody. Among those autoimmune myopathy cases, that are associated with autoantibodies, we can detect anti-SRP autoantibody positive myositis cases. We describe the role of signal recognition particle, also its structure and role in protein biosynthesis. We review how the necrotizing autoimmune myopathy is identified, what kind of differences are presented in relationship with the classical polymyositis cases. As we will see the anti-SRP titer correlates with the activity of the disease. We serve some examples from the literature how the disease looks in the childhood and also some rare cases from the literature. At the end of our review we present a case report to draw attention to the importance of the disease.]

Lege Artis Medicinae

OCTOBER 20, 2011

[Pulmonary arterial hypertension in systemic autoimmune diseases]

VÉGH Judit, ZEHER Margit

[Pulmonary arterial hypertension is a rare disease, but it occurs more often in systemic autoimmune diseases, where it represents one of the most severe, life-threatening complications. Its development is due to an immunoregulatory disorder characteristic to systemic diseases, persistent inflammation and the subsequent endothelial dysfunction, the presence of pathogenic autoantibodies, smooth muscle cell dysfunction and complex angiogenetic disorder. As a consequence of endothelial cell dysfunction, the balance between regulatory factors of vasoconstriction and vasodilation is disrupted. Intimal hyperplasia, endothelial cell proliferation, media hypertrophy and local thrombus formation can be observed and one of the main pathomorphological characteristic features, plexiform lesion develops, leading to obliterative vasculopathy. A more severe form of the disease develops in systemic sclerosis, which is explained by the main pathophysiological elements of scleroderma, namely immunoregulatory disorder, vasculopathy and fibroblast dysfunction. It is not easy to monitor the disease in these cases, because the deterioration can be caused by many other factors as well. Therefore, beseides the usual examinations, biomarkers and screening methods have a significant role. Treatment is not simple either, since no wellapplicable algorithms are available. In many disorders (systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis), effective immunosuppressive therapy started in time is crucial, whereas in case of systemic sclerosis, the principles of therapy applied for the idiopathic form should be followed.]

Hungarian Immunology

JANUARY 20, 2003

[Importance of Raynaud’s phenomenon in the connective tissue diseases]

CZIRJÁK László, NAGY Zoltán

[In the presence of Raynaud’s phenomenon compression syndromes, vibration, disorders causing hyperviscosity or arterial lesion and drog induced vasospasm should be excluded. In the background of unilateral Raynaud’s phenomenon organic, morphological abnormalities are present. Raynaud's phenomenon may also be the first symptom of connective tissue diseases, therefore the follow up of these cases is required. In case of patients with primary Raynaud’s phenomenon, the probability of developing a connective tissue diseases is very low. In the presence of antinuclear antibody positivity and/or scleroderma capillary pattern by capillarmicroscopy, the follow up is important, because these cases may develop a connective tissue disease, which predominantly belong to the scleroderma family. Simultaneous presence of Raynaud’s phenomenon and inflammation also strongly indicates that a connective tissue disease may later develop.]

Hungarian Immunology

JUNE 20, 2006

[Detection of rare phospholipid/co-factor antibodies in lupus patients]

TARR Tünde, KISS Emese, BÓTYIK Balázs, TUMPEK Judit, SOLTÉSZ Pál, ZEHER Margit, SZEGEDI Gyula, LAKOS Gabriella

[OBJECTIVE - Was to detect the rare phospholipid/ co-factor autoantibodies in lupus patients. PATIENTS AND METHODS - In the present study, besides anti-cardiolipin and anti-β2-glycoprotein I, antibodies directed against phosphatidil-serine, protrombin and annexinV were measured by commercial ELISA kits in 85 randomly selected lupus patients, 14 of whom met the criteria of antiphospholipid syndrome. Corralations were determined between the presence and concentration of rare antiphospholipids and those included in the diagnostic criteria of antiphospholid syndrome, as well as with clinical thrombotic manifestations. RESULTS - Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in eight, anti-β2GPI IgG in four and IgM in five patients. Lupus anticoagulant was detected in nine cases. Seven patients were positive for anti-phosphatidilserine IgG, nine for aPS IgM, anti-protrombin IgG was positive in nine cases. Antiprotrombin IgM and anti-annexinV were negative in all patients. Correlation was found between antiphosphatidilserine and anti-cardiolipin antibodies. The frequency and the concentration of rare antiphospholipid/ co-factor antibodies were higher in patients with secondray antiphospholipid syndrome. The presence of such rare antiphospholipid antibodies cumulated in patients with antiphospholipid syndrome. Their presence increased the frequency of thrombotic events in the entire study population, furthermore in those positive for lupus anticoagulant or anti-cardiolipin. CONCLUSIONS - The rare anti-phospholipid/cofactor antibodies were found in 12% of an unselected cohort of lupus patients. Their presence was more frequent in patients with secondary antiphospholipid syndrome, and further increased the risk of thrombotic complications.]

Hungarian Immunology

APRIL 20, 2003

[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

MARCH 20, 2006

[Clinical and immunoserological characteristics of mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH)]

VÉGH Judit, CSÍPŐ István, UDVARDY Miklós, KAPPELMAYER János, LAKOS Gabriella, ALEKSZA Magdolna, ZEHER Margit, SZEGEDI Gyula, BODOLAY Edit

[INTRODUCTION - The authors investigated the clinical characteristics, survival, accumulated damage index and immunoserological abnormalities in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS - Anti-U1RNP autoantibodies, anti-endothelial cell antibodies, anti-cardiolipin antibodies and serum trombomodulin as well as von Willebrand factor antigen concentrations were measured in 25 patients with MCTD associated with PAH (11 right heart catheterization and 14 Doppler echocardiography) and in 154 MCTD patients without PAH. Changes in arterial pulmonary pressure were followed up by echocardiography. RESULTS - In the 25 patients PAH followed MCTD diagnosis in the average 11.6±4.5 years of the diseases. The probability of survival was lower in MCTD patients with PAH than in the 154 non-PAH MCTD patients (five years survival rate in MCTD with PAH: 73.39%, vs. 96.43% in non PAH MCTD; p<0.01; 10 years survival rate 86.74% vs. 93.25%; p<0.01). Anti-endothelial cell antibodies were more frequently present in MCTD patients sera with PAH than in non PAH MCTD (p<0.001). Serum trombomodulin and vWFAg levels were higher in MCTDPAH patients than in non PAH MCTD patients (trombomodulin:34.2±15.3 ng/ml vs. 11.8±6.5 ng/ml; p<0.001; vWFAg: 311.1±147% vs. 172.5± 141%. Significant correlations were noticed between the quantity of anti-endothelial cell antibodies and serum trombomodulin level (r=0.466) as well as the quantity of anti-endothelial cell antibodies and vWFAg serum level (r=0.550). CONCLUSION - Survival probability was worse for MCTD patients with PAH than for non PAH MCTD patients. Our results suggest that in MCTD the presence of anti-endothelial cell antibodies and endothelial cell activation may play a role in the development of pulmonary arterial hypertension and in the maintenance of obliterative vascular processes.]

Hungarian Immunology

JUNE 20, 2002

[Autoimmun thyroiditis presence in patient with Hodgkin’s disease in remission]

BÍRÓ Edit, BAKÓ Gyula, SZEGEDI Gyula, ILLÉS Árpád

[INTRODUCTION - It is known that the incidence of hypothyroidism is higher in long term survivor patients with Hodgkin's disease, and it is supposed to be the result of treatment, such as neck radiotherapy. The author believe that other etiologic factors may also play a role in the development of hypothyroidism. PATIENTS AND METHODS - Looking for the possible causes of hypothyroidism, the thyroid function of 151 patients treated for Hodgkin's disease since 1970 were examined. These patients with Hodgkin's disease in complete remission for at least one year and their data on thyroid autoantibody positivity [antithyroid peroxidase antibody (aTPO), antihuman thyroglobulin antibody (aHTG), TSH antireceptor antibody (TRAK)] were analysed. RESULTS - Among the patients with antibody positive 26 received ultrasound scanning and fine needle aspiration cytology of the thyroid, which confirmed autoimmun thyroiditis. There were no significant differences between the mean age, histologic subtypes and stage of the disease between the patients with antibody positive those with antibody negative. A significantly greater number of women in the group of antibody positive patients was found and thyroid dysfunction (two cases of hyper, and 13 cases of hyperthyroidism) was revealed in 53.6% of the patients. Though antibody positivity was more frequent in patients having been treated by neck irradiation, but no significant relationship was found between the form of Hodgkin’s disease treatment and the development of thyroiditis. Thus the authors cannot confirm the assumption according to which the autoantigens released from the thyroid gland damaged by neck irradiation for Hodgkin's disease would provoke the development of thyroiditis. Since - independently of the type of treatment received - the incidence of thyroiditis is higher in patients with Hodgkin's disease, it is probable that immune regulation disorders may also play a role in its development and thus hypothyroidism is the result of a multi-factor process. DISCUSSION - These results underline the importance of a regular control of thyroid hormones and thyroid autoantibodies in follow up Hodgkin’s disease patients. Levothyroxine administered as an isohormone treatment may inhibit the development of hypothyroidism in patients with thyroiditis may improve the quality of their life.]

Lege Artis Medicinae

MARCH 20, 2005



[The authors provide a review on non-differentiated collagenosis (NDC) or, as it is called by another terminology, undifferentiated connective tissue disease (UCTD), outlining the clinical and serological alterations of the disease and give a definition of NDC. NDC is a pathological state when patients present clinical symptoms and serological alterations characteristic of a polysystemic autoimmune disease that cannot be explained by any other disease, where the symptoms however do not meet the diagnostic criteria of any other polysystemic autoimmune disease. NDC is a dynamic state and in 25-30% of the cases it may differentiate into CTD but in 40- 50% it remains in NDC stage and in 10-20% of the cases the patient may achieve remission. Differentiation is most frequent in the first two years of NDC. Patients should be treated and followed up in NDC state as well. The NDC stage is very important, since with the discovery of new autoantibodies, by employing new gene technology and by the follow-up and the treatment of the patients, our main aim is the earliest possible detection of differentiation into a definite polysystemic disease.]