Beáta Tóth

Publications (45)129.52 Total impact

• Article: Molecular mechanisms of mucocutaneous immunity against Candida and Staphylococcus species.

  László Maródi, Sophie Cypowyj, Beáta Tóth, Liudmyla Chernyshova, Anne Puel, Jean-Laurent Casanova
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  ABSTRACT: Signal transducer and activator of transcription (STAT) proteins are key components of the innate and adaptive immune responses to pathogenic microorganisms. Recent research on primary immunodeficiency disorders and the identification of patients carrying germline mutations in STAT1, STAT3, and STAT5B have highlighted the role of human STATs in host defense against various viruses, bacteria, and fungi. Mutations in STAT1 and STAT3 disrupt various cytokine pathways that control mucocutaneous immunity against Candida species, especially Candida albicans, and Staphylococcus species, especially Staphylococcus aureus. Here we consider inborn errors of immunity arising from mutations in either STAT1 or STAT3 that affect mucocutaneous immunity to Candida and Staphylococcus species.
  The Journal of allergy and clinical immunology 10/2012; · 9.17 Impact Factor
• Article: Herpes in STAT1 gain-of-function mutation [corrected].

  Beáta Tóth, Leonóra Méhes, Szilvia Taskó, Zsuzsanna Szalai, Zsolt Tulassay, Sophie Cypowyj, Jean-Laurent Casanova, Anne Puel, László Maródi
  The Lancet 06/2012; 379(9835):2500. · 38.28 Impact Factor
• Article: Genetic Variability of Central European Isolates of the Fusarium graminearum Species Complex

  Beáta Tóth, Ákos Mesterházy, Zoltán Horváth, Tibor Bartók, Mónika Varga, János Varga
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  ABSTRACT: The main causative agents of Fusarium head blight in central Europe are Fusarium graminearum and F. culmorum. We examined the mycotoxin producing ability, aggressiveness and molecular variability of F. graminearum isolates. Altogether twenty-six Hungarian, three Austrian isolates and representatives of eight species identified in the F. graminearum species complex were involved in this study. Mycotoxin producing abilities of the isolates were tested by GC-MS and HPLC. The central European isolates were found to belong to chemotype I (producing deoxynivalenol). Most isolates produced more 15-acetyl-deoxynivalenol than 3-acetyl-deoxynivalenol suggesting that they belong to chemotype Ib. All F. graminearum isolates were found to be highly pathogenic in in vitro aggressiveness tests. Phylogenetic analysis of random amplified polymorphic DNA profiles, and restriction profiles of the intergenic spacer region of the ribosomal RNA gene cluster of the isolates allowed clustering of the central European isolates into 17 and 16 haplotypes, respectively. When RAPD and IGS-RFLP data were combined, almost every single central European F. graminearum isolate could be differentiated (27/29 haplotypes). Sequence analysis of a putative reductase gene of some isolates was also performed. Based on molecular data, the majority of the central European isolates belonged to F. graminearum sensu stricto characteristic to the northern hemisphere, with the exception of one Hungarian isolate, which was not related to any known species of the F. graminearum species complex based on sequence data. The taxonomic assignment of two other Hungarian isolates, previously suggested as belonging to F. boothii based on mitochondrial DNA restriction profiles, was supported by sequence analysis.
  European Journal of Plant Pathology 04/2012; 113(1):35-45. · 1.41 Impact Factor
• Article: [Enzyme replacement therapy for Gaucher disease introduced in late adulthood].

  Pálma Juhász, Beáta Tóth, László Maródi, Melinda Erdos
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  ABSTRACT: Gaucher disease is the most prevalent lysosomal storage disorder caused by recessive mutation of the beta-glucocerebrosidase gene, which leads to massive lysosomal accumulation of glucocerebrosids especially in macrophages of bone marrow, liver and spleen. The most common presenting signs and symptoms are hepatosplenomegaly, bone pain, pathologic fractures, fatigue, bleeding tendency and recurrent infections. Regular enzyme replacement therapy which is available since 1992 in Hungary successfully reverses the symptoms of the disorder, including hematological abnormalities, bone infiltration and hepatosplenomegaly. Authors present here two cases diagnosed in late adulthood to emphasize the importance of early diagnosis and treatment.
  Orvosi Hetilap 02/2012; 153(7):264-70.
• Source

  Available from: Akos Mesterházy

  Article: Role of fungicides, application of nozzle types, and the resistance level of wheat varieties in the control of Fusarium head blight and deoxynivalenol.

  Akos Mesterházy, Beáta Tóth, Monika Varga, Tibor Bartók, Agnes Szabó-Hevér, László Farády, Szabolcs Lehoczki-Krsjak
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  ABSTRACT: Fungicide application is a key factor in the control of mycotoxin contamination in the harvested wheat grain. However, the practical results are often disappointing. In 2000-2004, 2006-2008 and 2007 and 2008, three experiments were made to test the efficacy of fungicide control on Fusarium Head Blight (FHB) in wheat and to find ways to improve control of the disease and toxin contamination. In a testing system we have used for 20 years, tebuconazole and tebuconazole + prothioconazole fungicides regularly reduced symptoms by about 80% with a correlating reduction in toxin contamination. Averages across the years normally show a correlation of r = 0.90 or higher. The stability differences (measured by the stability index) between the poorest and the best fungicides are about 10 or more times, differing slightly in mycotoxin accumulation, FHB index (severity) and Fusarium damaged kernels (FDK). The weak fungicides, like carbendazim, were effective only when no epidemic occurred or epidemic severity was at a very low level. Similar fungicide effects were seen on wheat cultivars which varied in FHB resistance. In this study, we found three fold differences in susceptibility to FHB between highly susceptible and moderately resistant cultivars when treated with fungicides. In the moderately resistant cultivars, about 50% of the fungicide treatments lowered the DON level below the regulatory limit. In the most susceptible cultivars, all fungicides failed to reduce mycotoxin levels low enough for grain acceptance, in spite of the fact that disease was significantly reduced. The results correlated well with the results of the large-scale field tests of fungicide application at the time of natural infection. The Turbo FloodJet nozzle reduced FHB incidence and DON contamination when compared to the TeeJet XR nozzle. Overall, the data suggest that significant decreases in FHB incidence and deoxynivalenol contamination in field situations are possible with proper fungicide applications. Additionally, small plot tests can be used to evaluate the quality of the field disease and toxin production.
  Toxins. 11/2011; 3(11):1453-83.
• Article: Molecular diagnostic challenges and complex management of consecutive twin pregnancies in a family with CD40 ligand deficiency.

  Olga Török, Beáta Tóth, Melinda Erdős, Gabriella Csorba, Edit Gyimesi, István Balogh, Zoltán Tóth, László Maródi
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  ABSTRACT: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency disorder caused by mutation in the gene encoding the CD40 ligand (CD40L) expressed on activated T cells. Prenatal genotyping in carriers with twin pregnancies is more challenging than in women with single pregnancies. In addition, women with twin pregnancies may decide on selective termination for which the risk of loss of the healthy fetus may exceed 7%. We report here on a family affected by XHIGM. Diagnosis of the disease was made in a male patient as late as 33 years of age. After family screening the sister of the proband conceived male twins in 2 consecutive pregnancies. In the first pregnancy, one of the male fetuses was hemizygous for the c.521A>G (Q174R) mutation in the CD40L gene. In the second pregnancy, ultrasound scan showed one fetus to have exencephaly and karyotyping revealed this fetus to have trisomy 18. Several options were discussed, but the parents decided on selective termination in both pregnancies. The interventions were successful in both cases and the mother now has two healthy sons. This report demonstrates the way in which advanced technologies in molecular medicine and obstetric interventions may assist families with decisions about possible selective termination in cases of life-threatening molecular or chromosomal disorders. The diagnosis of CD40L deficiency at the age of 33 year in the proband was striking and indicated that PIDs are still neglected as disease entities in the evaluation of patients with recurrent severe infectious diseases.
  Scandinavian Journal of Immunology 09/2011; · 2.23 Impact Factor
• Article: Response to letter to the editor on 'Fumonisin contamination and fumonisin producing black Aspergilli in dried vine fruits of different origin published in International Journal of Food Microbiology, 143:143-149'

  János Varga, Sándor Kocsubé, Beáta Tóth, Tibor Bartók
  International journal of food microbiology 09/2011; · 3.01 Impact Factor
• Article: BTK gene mutation in two non-identical twins with X-linked agammaglobulinemia associated with polyarticular juvenile idiopathic arthritis.

  Andrea Váncsa, Beáta Tóth, Zoltán Szekanecz
  The Israel Medical Association journal: IMAJ 09/2011; 13(9):579-80. · 1.02 Impact Factor
• Article: Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome.

  Vera Gulácsy, Tomas Freiberger, Anna Shcherbina, Malgorzata Pac, Liudmyla Chernyshova, Tadej Avcin, Irina Kondratenko, Larysa Kostyuchenko, Tatjana Prokofjeva, Srdjan Pasic, Ewa Bernatowska, Necil Kutukculer, Jelena Rascon, Nicolae Iagaru, Cinzia Mazza, Beáta Tóth, Melinda Erdos, Mirjam van der Burg, László Maródi
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  ABSTRACT: The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. WAS is caused by mutations in the WASP gene which encodes WASP, a 502-amino acid protein. WASP plays a critical role in actin cytoskeleton organization and signalling, and functions of immune cells. We present here the results of genetic analysis of patients with WAS from eleven Eastern and Central European (ECE) countries and Turkey. Clinical and haematological information of 87 affected males and 48 carrier females from 77 WAS families were collected. The WASP gene was sequenced from genomic DNA of patients with WAS, as well as their family members to identify carriers. In this large cohort, we identified 62 unique mutations including 17 novel sequence variants. The mutations were scattered throughout the WASP gene and included single base pair changes (17 missense and 11 nonsense mutations), 7 small insertions, 18 deletions, and 9 splice site defects. Genetic counselling and prenatal diagnosis were applied in four affected families. This study was part of the J Project aimed at identifying genetic basis of primary immunodeficiency disease in ECE countries. This report provides the first comprehensive overview of the molecular genetic and demographic features of WAS in ECE.
  Molecular Immunology 02/2011; 48(5):788-92. · 2.90 Impact Factor
• Article: Nijmegen breakage syndrome complicated with primary cutaneous tuberculosis.

  Melinda Erdös, Beáta Tóth, Imre Veres, Mária Kiss, Eva Remenyik, László Maródi
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  ABSTRACT: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosomal instability syndrome characterized by severe immunodeficiency, growth retardation, microcephaly, a distinct facial appearance, and a high predisposition to lymphoid malignancy. We report a 7-year-old white girl with NBS associated with cutaneous tuberculosis. The patient presented with multiple red-brown, centrally scaring plaques on the leg and had neither pulmonary nor systemic manifestation of tuberculosis. Polymerase chain reaction testing using Mycobacterium genus- and Mycobacterium tuberculosis species-specific primers confirmed the clinical diagnosis of cutaneous tuberculosis. This is the first report describing the simultaneous presentation of NBS and cutaneous tuberculosis.
  The Pediatric Infectious Disease Journal 10/2010; 30(4):359-60. · 3.58 Impact Factor
• Article: Alternaria hungarica sp. nov., a minor foliar pathogen of wheat in Hungary.

  Beáta Tóth, Mária Csosz, Agnes Szabó-Hevér, Emory G Simmons, Robert A Samson, János Varga
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  ABSTRACT: During routine wheat disease surveys in Hungary in 2007 Alternaria was isolated from leaf samples collected in Debrecen. Macro- and micro-morphological examinations and ITS sequence analyses indicated that the isolates represented a new Alternaria species, which we described as A. hungarica. The usually solitary conidia of A. hungarica resemble those of A. mouchaccae and A. molesta. However growth and sporulation pattern are more like those of A. geniostomatis and A. soliaridae. Phylogenetic analysis of ITS sequences indicated that this new species can be distinguished from all other examined Alternaria and Embellisia species. Pathogenicity tests indicated that A. hungarica can be considered a minor pathogen of wheat.
  Mycologia 09/2010; 103(1):94-100. · 2.03 Impact Factor
• Article: [Management of Fabry disease].

  Tamás Constantin, Annamária Székely, Andrea Ponyi, Vera Gulácsy, Csaba Ambrus, Krisztina Kádár, Ildikó Vastagh, Angéla Dajnoki, Beáta Tóth, Gergely Bokrétás, [......], Viktor Nagy, Pál Magyar, Mohamed Mahdi, Eva Rákóczi, Krisztina Németh, Dániel Bereczki, Miklós Garami, Melinda Erdos, László Maródi, György Fekete
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  ABSTRACT: Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group.
  Orvosi Hetilap 08/2010; 151(31):1243-51.
• Source

  Available from: Csaba Vágvölgyi

  Article: Chemical, physical and biological approaches to prevent ochratoxin induced toxicoses in humans and animals.

  János Varga, Sándor Kocsubé, Zsanett Péteri, Csaba Vágvölgyi, Beáta Tóth
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  ABSTRACT: Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard to animals and humans. Several strategies have been investigated for lowering the ochratoxin content in agricultural products. These strategies can be classified into three main categories: prevention of ochratoxin contamination, decontamination or detoxification of foods contaminated with ochratoxins, and inhibition of the absorption of consumed ochratoxins in the gastrointestinal tract. This paper gives an overview of the strategies that are promising with regard to lowering the ochratoxin burden of animals and humans.
  Toxins. 07/2010; 2(7):1718-50.
• Article: [Nijmegen Breakage syndrome].

  Melinda Erdos, Beáta Tóth, Pálma Juhász, Mohamed Mahdi, László Maródi
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  ABSTRACT: Nijmegen Breakage syndrome is a rare, autosomal recessive disorder characterized by severe, combined immunodeficiency, recurrent sinopulmonary infections, chromosomal instability, radiosensitivity, predisposition to malignancy, a "bird-like" facial appearance, progressive microcephaly, short stature, and mental retardation. The syndrome is caused by mutations in the NBS1 gene, which encodes a DNA-repair protein, named nibrin. The authors summarize current knowledge on molecular genetics, diagnostic characteristics and therapeutic options of this inborn error of innate immunity.
  Orvosi Hetilap 04/2010; 151(16):665-73.
• Article: [Fabry disease--diagnostic guideline].

  Tamás Constantin, Eva Rákóczi, Andrea Ponyi, Csaba Ambrus, Krisztina Kádár, Ildikó Vastagh, Angéla Dajnoki, Beáta Tóth, Gergely Bokrétás, Veronika Müller, [......], Sarolta Kárpáti, Viktor Nagy, Pál Magyar, Mohamed Mahdi, Krisztina Németh, Dániel Bereczki, Miklós Garami, Melinda Erdos, László Maródi, György Fekete
  [show abstract] [hide abstract]
  ABSTRACT: Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group.
  Orvosi Hetilap 02/2010; 151(7):243-9.
• Article: [Molecular diagnosis and therapeutic measures in patients with dyskeratosis congenita].

  Zsolt Reiger, Gergely Varga, Beáta Tóth, László Maródi, Melinda Erdos
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  ABSTRACT: Dyskeratosis congenita is a rare genetically heterogeneous disorder characterized by bone marrow failure and premature ageing. Current knowledge on clinical manifestations, molecular pathomechanisms, diagnostic criteria and therapeutic possibilities of patients with dyskeratosis congenita are described. Mutation analysis of the gene encoding for dyskerin revealed the c.IVS2-5C>G splice site mutation. The importance of early diagnosis in order to prevent severe invasive infections and non-infectious complications is emphasized. Family screening is important to identify carriers as prenatal genetic diagnosis conveys great benefits for family planning.
  Orvosi Hetilap 02/2010; 151(8):285-92.
• Article: Novel sequence variation of AIRE and detection of interferon-omega antibodies in early infancy.

  Beáta Tóth, Anette S B Wolff, Zita Halász, Attila Tar, Péter Szüts, István Ilyés, Melinda Erdos, Gyula Szegedi, Eystein S Husebye, Margit Zeher, László Maródi
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  ABSTRACT: Autoimmune polyendocrine syndrome type I (APS I) is a rare primary immunodeficiency disorder characterized by chronic mucocutaneous candidiasis, multi-organ autoimmunity and ectodermal dysplasia. Autoantibodies to parathyroid and adrenal glands and type I interferons (IFN) are hallmarks of APS I, which results from mutations in the autoimmune regulator (AIRE) gene. We wished to study clinical, immunological and genetic features of APS I in Hungarian patients, and to correlate anti-IFN-omega serum concentration with APS I and other multi-organ autoimmune diseases. Detailed analysis of patients with APS I and multi-organ autoimmune diseases. Seven patients with APS I and 11 patients with multi-organ autoimmune diseases were studied. Mutational analysis was performed by bidirectional sequencing of AIRE. Antibodies against IFN-omega and endocrine organ-specific autoantigens were studied with radioimmunoassay. RFLP was performed by digestion of DNA with Hin6I restriction enzyme. AIRE sequence analysis revealed homozygous c.769C>T mutations in three patients and compound heterozygous sequence variants (c.769C>T/c.44_66dup26bp; c.769C>T/c.965_977del13bp; c.769C>T/c.1344delC) in four patients with APS I. All the six live patients tested had markedly elevated IFN-omega antibodies, which were not found in heterozygous siblings or parents. One of the identified patients was negative for antibodies against IFN-omega at 6 weeks of age, but became positive at 7 months. At age 1, he is still without symptoms of the disease. In contrast to patients with APS I, no AIRE mutation or elevation of IFN-omega antibodies were detected in patients with multi-organ autoimmune diseases. This is the first overview of patients diagnosed with APS I in Hungary. A novel c.1344delC mutation in AIRE was detected. Anti-IFN-omega antibodies seem to appear very early in life and are helpful to differentiate APS I from other multi-organ autoimmune diseases.
  Clinical Endocrinology 10/2009; 72(5):641-7. · 3.17 Impact Factor
• Article: Successful umbilical cord blood stem cell transplantation in a child with WHIM syndrome.

  Gergely Kriván, Melinda Erdos, Krisztián Kállay, Gábor Benyó, Agnes Tóth, János Sinkó, Vera Goda, Beáta Tóth, László Maródi
  European Journal Of Haematology 10/2009; 84(3):274-5. · 2.61 Impact Factor
• Source

  Available from: Zsuzsa Szondy

  Article: Over-expression of integrin beta3 can partially overcome the defect of integrin beta3 signaling in transglutaminase 2 null macrophages.

  Beáta Tóth, Zsolt Sarang, György Vereb, Ailiang Zhang, Sakae Tanaka, Gerry Melino, László Fésüs, Zsuzsa Szondy
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  ABSTRACT: Transglutaminase 2 (TG2) is a protein crosslinking enzyme with many additional biological functions. We have previously shown that in TG2(-/-) mice the in vivo clearance of apoptotic cells is defective leading to autoimmunity. TG2 contributes to the formation of phagocytic portals by binding to both integrin beta(3), a known phagocytic receptor, and its bridging molecule, MFG-E8. In TG2 null macrophages integrin beta(3) cannot accumulate around the apoptotic cells and its signaling is impaired. In the present study we describe a subline of TG2 null mice, in which a compensatory increase in integrin beta(3) expression, which resulted alone in a high receptor concentration around the apoptotic cells without the requirement for accumulation, partially corrected the defect in integrin beta(3) signaling. Our data provide a proof for the concept that the function of TG2 is to stabilize accumulated integrin beta(3) concentration in the phagocytic cup.
  Immunology letters 08/2009; 126(1-2):22-8. · 2.91 Impact Factor
• Article: Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: a cohort study.

  Beáta Tóth, Alla Volokha, Alexander Mihas, Malgorzata Pac, Ewa Bernatowska, Irina Kondratenko, Alexander Polyakov, Melinda Erdos, Srdjan Pasic, Michaela Bataneant, [......], Sonja Peova, Liudmyla Chernyshova, Ioan Gherghina, Margit Serban, Mary Ellen Conley, Luigi D Notarangelo, C I Edvard Smith, Jacques van Dongen, Mirjam van der Burg, László Maródi
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  ABSTRACT: Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.
  Molecular Immunology 07/2009; 46(10):2140-6. · 2.90 Impact Factor