The Cellular Immunology Group
Principal Investigator: Péter Antal-Szalmás MD, PhD
Members of the group:
Pal Bhattoa Harjit MD, PhD; Zoltán Mezei MD
Technician: Róza Földesi Varga BSc; Gabriella Szabó Gaál BSc
The human body is constantly attacked by invading pathogenic microorganisms. The evolutionary ancient form of the host defense against these pathogens is the innate immune system. Toll-like receptors and their associated molecules like CD14 or LPS-binding protein (LBP) are the most important pattern recognition receptors of this system. They support the elimination of invading microorganisms, and have an important role in the initiation of the adaptive immune response and even can participate in the development of autoimmune disorders.
One major area of our interest is the characterization of the expression, function and interaction of LBP, CD14 and the associated TLRs in human and mouse experimental systems. Furthermore, we analyze the expression and functions of these molecules in autoimmune diseases (SLE, poly/dermatomyositis, systemic sclerosis) and in immune mediated skin disorders (atopic dermatitis) and gastroenterological disorders characterized by frequent/infrequent bacterial infections. We also study the distribution of SNPs of CD14, TLR2, TLR4 and several cytokine genes in these diseases. The aim of these studies is to find serum or genetic markers that can characterize the clinical properties of certain immunological disorders. In this field, we have a long-lasting cooperation with the Clinical Immunology and Gastroenterological Departments of the Institute of Internal Medicine.
The second aim of our group is to develop new antimicrobial fusion proteins. Misuse of existing antibiotics and the lack of development of new antibiotics have resulted in the development of (multi)resistance in bacteria, fungi and viruses. To fight infectious diseases effectively in the future we have to broaden the approaches in therapeutic intervention. The fusion molecules we create consist of the active domain of different antimicrobial proteins and the Fc portion of human immunoglobulin G. In this way we hope to create general opsonins that are able to bind to different microorganisms and to kill these pathogens. This work is done in cooperation with the group of Dr. Jos van Strijp (EWI, Utrecht University, the Netherlands).
We utilize mostly flow cytometric, ELISA, indirect immunofluorescence and Western-blot techniques and we perform PCR-RFLP, Taqman-probes or sequencing based SNP analysis. We have some experiences in protein purification, labeling, cloning and expression, too.
Papp M, Sipeki N, Vitalis Zs, Tornai T, Altorjay I, Tornai I, Udvardy M, Fechner K, Jacobsen S, Teegen B, Sumegi A, Veres G, Lakatos PL, Kappelmayer J, Antal-Szalmas P: High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis. J. Hepatology, accepted for publication, 2013
Vida A, Bardoel B, Milder F, Majoros L, Sümegi A, Bácsi A, Vereb G, van Kessel KP, van Strijp JA, Antal-Szalmás P: Fusion of the Fc part of human IgG1 to CD14 enhances its binding to gram-negative bacteria and mediates phagocytosis by Fc receptors of neutrophils. Immunol Lett. 2012, 146:31-39
Bhattoa HP, Nagy E, More C, Kappelmayer J, Balogh A, Kalina E, Antal-Szalmas P: Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age: the HunMen Study. Osteoporos Int. 2013, 24:179-186
Papp M, Vitalis Z, Altorjay I, Tornai I, Udvardy M, Harsfalvi J, Vida A, Kappelmayer J, Lakatos PL, Antal-Szalmas P: Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections. Liver Int. 2012, 32:603-611
Bubán T, Koczok K, Földesi R, Szabó G, Sümegi A, Tanyi M, Szerafin L, Udvardy M, Kappelmayer J, Antal-Szalmás P: Detection of internal tandem duplications in the FLT3 gene by different electrophoretic methods. Clin Chem Lab Med. 2011, 50:301-310
Vida A, Troelstra A, Antal-Szalmás P, van Bommel TJ, Verheul AF, Verhoef J, van Kessel KP, van Strijp JA: Neutralization of Neisseria meningitidis outer membrane vesicles. Inflamm Res. 2011, 60:801-805
Szekanecz E, Szucs G, Szekanecz Z, Tarr T, Antal-Szalmás P, Szamosi S, Szántó J, Kiss E: Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: associations with organ manifestations, immunolaboratory markers and disease activity indices. J. Autoimmun. 2008, 31:372-376
Kappelmayer J, Udvardy M, Antal-Szalmas P: Pgp and FLT3: identification and modulation of two proteins that lead to chemotherapy resistance in acute myeloid leukemia. Curr. Med. Chem. 2007, 14:519-530
Sumegi A, Szegedi Gy Gal M, Hunyadi J, Antal-Szalmas P: Analysis of components of the CD14/TLR system on leukocytes of patients with atopic dermatitis. Int. Arch. Aller. Immunol, 2007, 143, 177-184
Antal-Szalmas P, Sumegi A, Aleksza M, Kovacs I, Sipka S, Zeher M, Kiss E, Szegedi Gy: Glucocorticosteroid therapy decreases CD14-expression and CD14-mediated LPS-binding and activation of monocytes in patients suffering from Systemic Lupus Erythematosus. Clin. Immunol. 2005, 117., 271-279
Antal-Szalmas P, Poppelier, Sumegi A, T. van der Bruggen, J. Verhoef, K.P.M. van Kessel, J.A.G. van Strijp: Spare CD14 molecules on human monocytes enhance the sensitivity for low LPS concentrations. Immunol. Let. 2004, 93, 11-15
Antal-Szalmas P: Evaluation of CD14 in host defense. Eur. J. Clin. Invest. 2000, 30, 167-179
Projects in Oncology
Péter Antal-Szalmás MD, PhD, Zoltán Steiber BSc: Comparative examination of plasma proteins of cancerous and non-cancerous individuals using monoclonal antibody based microchips. (in cooperation with the BioSystems International Ltd.)
Péter Antal-Szalmás MD, PhD, Gabriella Szabó Gaál BSc, Róza Földesi Varga BSc: Identification and characterization of molecular mechanisms involved in the development of resistance against FLT3-inhibitors.