Hungarian Immunology

[Mosaic of Autoimmunity]

SZEKANECZ Zoltán

JANUARY 22, 2008

Hungarian Immunology - 2008;7(01-02)

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Hungarian Immunology

[The role of endothelium, cell migration, chemokines and angiogenesis in inflammatory rheumatic diseases]

BESENYEI Tímea, PÁKOZDI Angéla, VÉGVÁRI Anikó, SZABÓ Zoltán, SZEKANECZ Zoltán

[Endothelial cells, leukocyte-endothelial interactions and angiogenesis are highly involved in the pathogenesis of inflammation and thus in that of inflammatory rheumatic diseases. As this research area is very progressive, one needs to review novel molecular mechanisms and new therapeutic approaches in this respect. Authors review the most important functions of endothelial cells, the process of leukocyte extravasation, tissue infiltration and their cellular and molecular basis. Endothelial cells themselves produce a number of inflammatory mediators including interleukin-1 (IL-1), IL-6, IL-8, chemokines and others. Among cell adhesion molecules, β1 and β3 integrins, as well as E-, L- and P-selectins and their respective ligands have been implicated in leukocyte-endothelial adhesion. In recent years, numerous inflammatory mediators, cytokines, chemokines and proteases have been implicated in angiogenesis and angiostasis. Hypoxia, the vascular endothelial growth factor (VEGF)-angiopoietin system and mechanisms driven by β3 integrins are of major importance during angiogenesis. Significant amount of data have become available of the regulation of cell adhesion, migration and neovascularisation. Adhesion, chemokine and angiogenesis research has important clinical, practical aspects for antirheumatic and anti-cancer therapy. VEGF antagonists, anti-integrin antibodies, chemokine and chemokine receptor inhibitors, as well as thalidomide are currently in the first line of development.]

Hungarian Immunology

[Kinetic measurement on flow cytometer simultaneous monitoring of intracellular progresses]

MÉSZÁROS Gergő, RÓNAI Katalin Zsuzsanna, TOLDI Gergely, KAPOSI Ambrus, VÁSÁRHELYI Barna, TRESZL András

[INTRODUCTION - Flow cytometry provides an opportunity for real-time monitoring of intracellular processes in several cell populations simultaneously. Cells stained with specific fluorescent dyes are sequentially measured during kinetic FACS measurements. Fluorescent light signals obtained in cells are recorded and analyzed to describe the alteration of the investigated parameter(s) over time. The use of kinetic FACS assays is not spread as there was no mathematic algorithm to characterize objectively the distribution of data and kinetic changes. MATERIALS, METHODS, RESULTS - We developed a new approach which fits functions to measured data sets, describes the statistical distribution and forms a basis for statistical comparison between individual kinetic measurements. We created two FACS assays on BD FACS Aria instrument. The first one monitors calcium flux, generation of reactive oxygen species and mitochondrial membrane potential, while the second one monitors mitochondrial calcium flux, nitric oxide generation and plasma membrane potential in CD4+ and CD8+ lymphocytes simultaneously before and after the administration of a lymphocyte activator. CONCLUSIONS - This technique may be used to investigate purposes (i.e. to test the impact of any agent (such as immunmodulatory drugs) on cellular processes in lymphocytes) and to diagnostic purposes (i.e. to test the alteration of lymphocyte activation characteristics in disease).]

Hungarian Immunology

[MCP-1 (monocyte chemoattractant protein-1) G/A and T-bet (T-helper promoter factor) C/G polymorphisms in primary Sjögren’s syndrome and systemic lupus erythematosus]

KOVÁCS Attila, KONCZ Ágnes, ENDREFFY Emőke, ARANKA László, PETRI Ildikó, ELLER József, SZALAI Csaba

[INTRODUCTION - Monocyte chemoattractant protein- 1 (MCP-1) is a β-chemokine involved in the attraction and accumulation of mononuclear granulocytes towards the site of inflammation. One of the transcriptional factors of T-cells is called T-bet. PATIENTS AND METHODS - The authors investigated the MCP-1-2518 G/A and T-bet 310 C/G (His33Gln) polymorphisms evaluating the distribution of the specific genotypes in 45 patients with primary Sjögren's syndrome (pSS), 51 patients with systemic lupus erythematosus (SLE), and in 320 healthy blood donors as the control group. MCP-1-2518 G/A and T-bet 310 C/G polymorphisms were detected with molecular genetic methods from the purified genomic DNA. RESULTS - The frequency of the MCP-1-2518 AG heterozygous genotype decreased tendentiously only in SLE patients, while the frequency of the MCP-1 AA homozygous genotype increased comparing to the control group (13.7% vs. 5.9%; Pearson’s χ2 test=6.125, ns.). Analyzing the genotype frequency for the MCP-1 wild (GG) and AA homozygous genotypes in pSS group, the MCP-1 AA homozygous genotype proved to be more frequent comparing to the control group (82.8%:17.2% vs. 90.7%:9.3%; Pearson’s χ2 test 1.755, ns). These relations showed only tendentious association in the SLE group (81.6%:18.7% vs. 90.7%:9.3%; Pearson’s χ2 2.811, p=0.094, ns.) There was not any significant correlation between the investigated MCP-1- 2518 G/A and the T-bet 310 C/G polymorphisms and the TNF-α -308 G/A and -238 allele polymorphisms. The frequency of T-bet was equal in relation with heterozygous (CG) to wild CC genotype in the investigated two autoimmune disorders. The GG homozygous genotype for T-bet could not be found in SLE and pSS groups, likely to be a protective factor. CONCLUSIONS - The above mentioned polymorphisms didn’t show any significant correlation with TNF-α -308 and -238 allele polymorphisms. The further research of the MCP-1 G/A and T-bet C/G polymorphisms is important, because of their possible prognostic importance for SLE and pSS.]

Hungarian Immunology

[Pseudolymphoma orbitae]

VÁNCSA Andrea, GERGELY Lajos, NEMES Zoltán, BÍRÓ Edit, ILLÉS Árpád, BAKÓ Gyula

[INTRODUCTION - Pseudolymphoma orbitae is a rare and difficult entity. The cooperation of the pathologist and clinician is needed to properly manage the patient. CASE REPORT - The authors report the case history of a 38 years old male patient. His disease started at the age of 30. He was previously treated with allergic rhinitis. No definitive diagnosis was made for eight years. Several surgical biopsies were made from nasal mucosa, but no specific histologyical diagnosis was applicable. At the age of 30 he developed an unilateral exophthalmus on the left side. Thyroid associated ophthalmopathy was ruled out several times with laboratory analysis. High dose methylprednisone therapy was repeatedly given with limited results. At the age of 34 orbital CT and MRI scan confirmed the pseudotumour orbitae already compressing the optical nerve. Laboratory analysis again ruled out thyroid associated ophthalmopathy. Churg-Strauss syndrome, Wegener’s granulomatosis or Sjögren’s syndrome could be ruled out. A bone marrow trephine biopsy excluded systemic hematological disease as well. A biopsy was performed from the retrobulbar mass again, which confirmed the lymphoid hyperplasia with B-cell dominance. High dose methylprednisone and local irradiation resulted only moderate decrease of the mass, so systemic chemotherapy was started using CVP (cyclophosphamide, vincristin, prednisone) then CHOP (CVP + anthrycycline) polychemotherapy for eight cycles and subcutaneous interferon-α for 20 months. CONCLUSIONS - This resulted a complete regression of the disease, and the patient is well for 48 months now.]

Hungarian Immunology

[EULAR]

SZEKANECZ Zoltán

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Clinical Neuroscience

[Inclusion body myositis - a rarely recognized disorder]

DÉZSI Lívia, DANIELSSON Olof, GÁTI István, VARGA Edina, VÉCSEI László

[Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-β failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.]

Lege Artis Medicinae

[HUMAN DENDRITIC CELLS AND INFECTIVE AGENTS]

KIS Zoltán

[Dendritic cells represent important components of the innate and adaptive immune responses. Human dendritic cells can be divided into two major subsets: myeloid and plasmacytoid (lymphoid) dendritic cells. The unique function of the dendritic cells is to capture antigens, present and to activate the antigenic peptides to the T lymphocytes. Dendritic cells go through a maturation process both in vitro and in vivo. By the use of pathogenrecognition- receptors the immature dendritic cells sense diverse pathogens or their various components, or cellular factors produced by the infected neighboring non-dendritic cells, and maturation signals are transduced for the dendritic cells. The heterogeneity of the pathogen-recognition-receptors and the microbial stimuli initiate a broad range of interactions between dendritic cells and infectious agents. Dendritic cells infected with certain viruses produce only a few infectious particles, but express and present viral antigens to T lymphocytes and immune response is initiated (influenza virus). Dendritic cells infected with certain pathogens not only initiate immune response but also disseminate the pathogen (human immunodeficiency virus, Mycobacterium tuberculosis). Some pathogens are killed in the dendritic cells, but the antigens are presented to the T cells, and immune responses are induced (Chlamydia trachomatis and Chlamydia psittaci). Dendritic cells capture antigens produced by infected neighbouring cells and present them to T lymphocytes, thus immune response is initiated (human cyto-megalovirus, herpes simplex virus). Dendritic cells are responsible for virus-induced immunosupp-ression; dendritic cells infected with certain pathogens form syncytia with T cells, thereby contribute to the suppression of T cell functions directed against opportunistic infections (measles virus). Dendritic cells can present not only foreign antigens but also self-antigens and when immature dendritic cells become mature upon exposure to inflammatory processes or to pathogens capable of activating them they can induce autoimmunity.]

Lege Artis Medicinae

[The role of fathers in the family therapy of eating disorders, with special regard to mosaic families]

TÚRY Ferenc, SZENTES Annamária

[Eating disorders (anorexia nervosa, bulimia nervosa) are the typical forms of modern disorders of civilization. In the therapy of young (below age of twenty years) patients the family therapy can play a decisive role. During family therapy, in the case of mosaic families (newly organized families after divorce and second marriage) it is a frequent question, which family members should be involved into the therapeutical sessions: the biological parents, or the members of the actual families. In this paper two cases are reported where mosaic families were consulted. In the family therapy the new distribution of parental roles, the strengthening of the paternal responsibility of the foster-father were crucial in the families. In both cases a full remission occurred. As a conclusion we can state that during family therapy of eating disordered patients - and supposedly in other psychosomatic disorders - in the case of mosaic families the involvement of the actual family members, and the strengthening of the parental role can be an important factor in the therapeutical efficacy.]

Hungarian Immunology

[3rd International Congress of Autoimmunity - the congress report]

SZEKANECZ Zoltán

Hungarian Immunology

[On the role of aging in etiology of autoimmunity]

SEMSEI Imre, ZEHER Margit, BAKÓ Gyula

[Several types of diseases, among others autoimmune illnesses, could be coupled with the general processes of aging. The two-edged sword of the immune defense is directed once against environmental attacks and on the other side against the self. However, one has to make a difference between normal (physiological) clearance and autoimmune diseases, although both sides of autoimmunity are influenced by the general processes of senescence. Aging of the thymus seems to be one of the key elements of the etiology of autoimmunity, although other cell types and their aging also play a substantial role in this process. The spontaneous genetic instability, the acquired genetic mutations due to aging and the age-related alterations of the information level of the body together may be important elements of the patomechanism of both the physiological autoimmunity and the autoimmune diseases. Nevertheless, physiological autoimmunity seems to be directed mostly by natural factors (such as aging and apoptosis) but primary autoimmune diseases may be caused by genetic instability that is enhanced by aging as well.]