Karoly Palatka

Publications of Karoly Palatka

• Association of peroxisome proliferator-activated receptor gamma polymorphisms with inflammatory bowel disease in a Hungarian cohort.

  Authors: Szilard Poliska, Andras Penyige, Peter Laszlo Lakatos, Maria Papp, Karoly Palatka, Laszlo Lakatos, Tamas Molnar, Laszlo Nagy

  Inflammatory bowel diseases. 06/2011; 18(3):472-9.

  Inflammatory bowel disease (IBD) shows increasing incidence in the last few years in Eastern Europe, including Hungary. Since genetic susceptibility of patients plays an important role in theInflammatory bowel disease (IBD) shows increasing incidence in the last few years in Eastern Europe, including Hungary. Since genetic susceptibility of patients plays an important role in the development and pathogenesis of IBD, it is important to identify new susceptibility genes. Peroxisome proliferator-activated receptor gamma (PPARγ) is expressed in the colon and has protective effects against inflammatory processes. Our aim was to examine the association of four polymorphisms of PPARγ in a well-characterized Hungarian IBD cohort. In all, 575 Crohn's disease (CD), 103 ulcerative colitis (UC) patients, and 486 sex- and age-matched controls were examined. Four polymorphisms of PPARγ (rs10865710 [C-681G], rs2067819, rs3892175, and rs1801282 [Pro12Ala]) were genotyped by TaqMan genotyping assays. The Pro12Ala polymorphism showed significant association with CD when the frequencies of the homozygous variants (Pro/Pro vs. Ala/Ala) were compared. The minor Ala/Ala genotype was significantly less frequent in CD patients compared to the controls (odds ratio [OR] = 0.33; 95% confidence interval [CI] = 012-0.94; P = 0.03), suggesting a potential protective effect of the Ala allele. The GAGG haplotype of PPARγ confers a protective effect in CD; however, it is not significant, but in UC it has a protective effect with a significant level (OR = 0.14; 95% CI: 0.05-0.42; P = 3.78 × 10(-5) ), while GAGC increases the risk of UC (OR = 6.70; 95% CI: 3.41-13.17; P = 3.85 × 10(-10) ). In the present study we demonstrated a significant association between PPARγ polymorphisms and the development of CD and UC at single loci level and also in haplotype combinations. (Inflamm Bowel Dis 2012;).

• Serum lipopolysaccharide-binding protein and soluble CD14 are markers of disease activity in patients with Crohn's disease.

  Authors: Peter Laszlo Lakatos, Lajos Sandor Kiss, Karoly Palatka, Istvan Altorjay, Peter Antal-Szalmas, Eszter Palyu, Miklos Udvardy, Tamas Molnar, Klaudia Farkas, Gabor Veres, Jolan Harsfalvi, Janos Papp, Maria Papp

  Inflammatory bowel diseases. 03/2011; 17(3):767-77.

  In inflammatory bowel disease (IBD), enhanced inflammatory activity in the gut is thought to increase the risk of bacterial translocation and endotoxemia. In the present study we investigated theIn inflammatory bowel disease (IBD), enhanced inflammatory activity in the gut is thought to increase the risk of bacterial translocation and endotoxemia. In the present study we investigated the association between serum level of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and clinical disease activity, high-sensitivity C-reactive protein (hs-CRP), antimicrobial serology profile, NOD2/CARD15 status, and clinical phenotype in a large cohort of Hungarian Crohn's disease (CD) patients. In all, 214 well-characterized, unrelated, consecutive CD patients (male/female ratio: 95/119; age: 35.6 ± 13.1 years; duration:8.3 ± 7.5 years) and 110 healthy controls were investigated. Sera were assayed for LBP, sCD14, hs-CRP, ASCA IgG/IgA, anti-OMP IgA, and pANCA antibodies. NOD2/CARD15 and TLR4 variants were tested. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. Serum LBP level was significantly higher (P < 0.0001 for both), while sCD14 was lower (P < 0.0001) in both active and inactive CD compared to the controls. The accuracy of hs-CRP (area under the curve [AUC] = 0.66), sCD14 (AUC = 0.70), and LBP (AUC = 0.58) was comparable for identifying patients with active disease. There was a significant correlation between LBP (P < 0.001), sCD14 (P = 0.015), and hs-CRP levels but not with antimicrobial seroreactivity or NOD2/CARD15 genotype. In inactive CD, LBP was associated with penetrating disease. In a Kaplan-Meier analysis and a proportional Cox-regression analysis, LBP (P = 0.006), sCD14 (P = 0.007), and previous relapse frequency (P = 0.023) were independently associated with time to clinical relapse during a 12-month follow-up period. Serum LBP and sCD14 are markers of disease activity in CD with a similar accuracy as hs-CRP. In addition, LBP, sCD14, and a high frequency of previous relapses were independent predictors for 1-year clinical flare-up. (Inflamm Bowel Dis 2011).

• Phenotypic polymorphism of haptoglobin: a novel risk factor for the development of infection in liver cirrhosis.

  Authors: Zsuzsanna Vitalis, Istvan Altorjay, Istvan Tornai, Karoly Palatka, Sandor Kacska, Eszter Palyu, David Tornai, Miklos Udvardy, Jolan Harsfalvi, Tamas Dinya, Gabor Veres, Peter Laszlo Lakatos, Maria Papp

  Human immunology. 01/2011; 72(4):348-54.

  The α-chain alleles 1 and 2 of haptoglobin (Hp) molecule account for three phenotypes, which have biologically important differences in their antioxidant, scavenging, and immunomodulatory propertiesThe α-chain alleles 1 and 2 of haptoglobin (Hp) molecule account for three phenotypes, which have biologically important differences in their antioxidant, scavenging, and immunomodulatory properties and may thereby influence the course of inflammatory diseases. A follow-up observational study was conducted to assess the association between haptoglobin phenotype and the development of clinically significant bacterial infections in patients with liver cirrhosis. Sera of 336 patients with liver cirrhosis of various etiologies and 384 healthy subjects were investigated. Haptoglobin phenotypes were determined by gel electrophoresis and assigned corresponding genotype. Haptoglobin phenotype distributions of patients and controls was similar (Hp1-1: 10.7% vs 11.5%, Hp2-1: 47.9% vs 46.1% and Hp2-2: 41.4% vs 42.4%). The probability of clinically significant bacterial infections was calculated for each haptoglobin phenotype (Hp1-1: 50.0%, Hp2-1: 36.0% and Hp2-2: 26.6%, p = 0.039). In a logistic regression analysis, Hp1-1 phenotype (p = 0.015, OR: 2.74, 95% CI: 1.22-6.13), Child-Pugh stage (p = 0.038, OR: 1.40, 95% CI: 1.02-1.91) and presence of co-morbidities (p < 0.001, OR: 2.64, 95% CI: 1.63-4.27) were independently associated with infections. In a Cox regression analysis, Hp1-1 phenotype (p = 0.014), Child-Pugh stage C (p < 0.001), and presence of co-morbidities (p = 0.004) were associated with time to first infectious episode. Phenotypic haptoglobin polymorphism was independent predictor for risk and time to first clinically significant bacterial infectious episode.

• Association of adherence to therapy and complementary and alternative medicine use with demographic factors and disease phenotype in patients with inflammatory bowel disease.

  Authors: Peter Laszlo Lakatos, Zsofia Czegledi, Gyula David, Zsofia Kispal, Lajos S Kiss, Karoly Palatka, Tunde Kristof, Ferenc Nagy, Agnes Salamon, Pal Demeter, Pal Miheller, Tamas Szamosi, Janos Banai, Maria Papp, Laszlo Bene, Agota Kovacs, Istvan Racz, Laszlo Lakatos

  Journal of Crohn's & colitis. 09/2010; 4(3):283-90.

  Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patientsPrevious studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patients fail to comply with treatment. The aim of our study was to evaluate the prevalence of non-adherence and the use of CAM in Hungarian patients with IBD. A total of 655 consecutive IBD patients (CD: 344, age: 38.2 [SD 12.9]years; UC: 311, age: 44.9 [15.3]years) were interviewed during the specialist visit by self-administered questionnaire including demographic and disease-related data as well as items analyzing the extent of non-adherence and CAM use. Patients taking more than 80% of each prescribed medication were classified as adherent. The overall rate of self-reported non-adherence (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use did not differ between Crohn's disease (CD) and ulcerative colitis (UC). The most common causes of non-adherence were: forgetfulness (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%) and too frequent dosing. Most common forms of CAM were herbal tea (47.3%), homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease duration, date of last follow-up visit, educational level and previous surgeries were predicting factors for non-adherence. Alternative medicine use was associated in both diseases with younger age, higher educational level, and immunosuppressant use. In addition, CAM use in UC was more common in females and in patients with supportive psychiatric/psychological therapy. Non-adherence and CAM use is common in patients with IBD. Special attention should be paid to explore the identified predictive factors during follow-up visits to improve adherence to therapy and improving patient-doctor relationship.

• Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis.

  Authors: Istvan Altorjay, Zsuzsanna Vitalis, Istvan Tornai, Karoly Palatka, Sandor Kacska, Gyula Farkas, Miklos Udvardy, Jolan Harsfalvi, Tamas Dinya, Peter Orosz, Bela Lombay, Gabriella Par, Alajos Par, Timea Csak, Janos Osztovits, Ferenc Szalay, Antal Csepregi, Peter Laszlo Lakatos, Maria Papp

  Journal of hepatology. 09/2010; 53(3):484-91.

  Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly inMannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosis due to the relative immuncompromised state. Sera of 929 patients with various chronic liver diseases [autoimmune liver diseases (ALD), 406; viral hepatitis C (HCV), 185; and liver cirrhosis (LC) with various etiologies, 338] and 296 healthy controls (HC) were assayed for MBL concentration. Furthermore, a follow-up, observational study was conducted to assess MBL level as a risk factor for clinically significant bacterial infections in cirrhotic patients. MBL level and the prevalence of absolute MBL deficiency (<100 ng/ml) was not significantly different between patients and controls (ALD: 14.5%, HCV: 11.9%, LC: 10.7%, HC: 15.6%). In cirrhotic patients, the risk for infection was significantly higher among MBL deficient subjects as compared to non-deficient ones (50.0% vs. 31.8%, p=0.039). In a logistic regression analysis, MBL deficiency was an independent risk factor for infections (OR: 2.14 95% CI: 1.03-4.45, p=0.04) after adjusting for Child-Pugh score, co-morbidities, gender, and age. In a Kaplan-Meier analysis, MBL deficiency was associated with a shorter time to develop the first infectious complication (median days: 579 vs. 944, pBreslow=0.016, pLogRank=0.027) and was identified as an independent predictor in a multivariate Cox-regression analysis (p=0.003, OR: 2.33, 95% CI: 1.34-4.03). MBL deficiency is associated with a higher probability and shorter time of developing infections in liver cirrhosis, further supporting the impact of the MBL molecule on the host defense.

• Mannose-binding lectin level and deficiency is not associated with inflammatory bowel diseases, disease phenotype, serology profile, and NOD2/CARD15 genotype in a large Hungarian cohort.

  Authors: Maria Papp, Peter Laszlo Lakatos, Jolan Harsfalvi, Gyula Farkas, Karoly Palatka, Miklos Udvardy, Tamas Molnar, Klaudia Farkas, Ferenc Nagy, Gabor Veres, Laszlo Lakatos, Agota Kovacs, Tamas Dinya, Agnes Katalin Kocsis, Janos Papp, Istvan Altorjay

  Human immunology. 04/2010; 71(4):407-13.

  Mannose-binding lectin (MBL) is a major, soluble, pattern-recognition molecule and an important component of the innate host defense. The role of MBL in inflammatory bowel diseases (IBDs) isMannose-binding lectin (MBL) is a major, soluble, pattern-recognition molecule and an important component of the innate host defense. The role of MBL in inflammatory bowel diseases (IBDs) is controversial. We determined the prevalence of MBL deficiency in a Hungarian IBD patients' cohort, and whether it is associated with the antimicrobial antibody formation or particular clinical manifestations. Nine hundred ninety IBD patients and 225 healthy subjects were investigated. Sera were assayed for MBL and a panel of antimicrobial antibodies (anti-OMP, anti-Saccharomyces cerevisiae antibodies, and antiglycans) by ELISA. TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. Median MBL level was not significantly different between IBDs (Crohn's disease [CD]: 929; ulcerative colitis [UC]: 810 ng/ml) and the control group (1027 ng/ml), as well as the prevalence of absolute MBL deficiency (<100 ng/ml) (CD: 15.0%, UC: 18.4%, controls: 15.6%). The presence of a low MBL level (<500 ng/ml) was not associated with any of the examined serologic markers, or their combinations. In addition, there was no association with the clinical presentation, disease course, or response to treatment. TLR4 variant genotype was more common in CD patients without MBL deficiency (11% vs. 1.7%, OR: 7.29, 95% CI: 1.08-53.9, p = 0.02). We failed to confirm any association between MBL deficiency and serologic marker positivity. MBL deficiency was not predictive for clinical phenotype or disease activity in IBDs.

• Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets.

  Authors: Bertalan Mesko, Szilard Poliska, Andrea Szegedi, Zoltan Szekanecz, Karoly Palatka, Maria Papp, Laszlo Nagy

  BMC medical genomics. 01/2010; 3:15.

  Chronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, butChronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood. It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other. Diseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05). Here we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition. These findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.

• Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central Europe - a Hungarian nationwide observational study.

  Authors: Pal Miheller, Peter Lakatos, Gabor Horvath, Tamas Molnar, Tamas Szamosi, Zsofia Cegledi, Agnes Salamon, Jozsef Czimmer, Gyorgy Rumi, Karoly Palatka [......] Bela Hunyady, Laszlo Simon, Janos Papp, Janos Banai, Ferenc Nagy, Janos Lonovits, Laszlo Ujszaszy, Gyorgyi Muzes, Laszlo Herszenyi, Zsolt Tulassay

  BMC gastroenterology. 09/2009; 9(1):66.

  ABSTRACT: BACKGROUND: Infliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD), with efficacy in theABSTRACT: BACKGROUND: Infliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD), with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary. METHODS: During a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5mg/kg IFX infusions given at week 0, 2 and 6) at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy. RESULTS: Three hundred and sixty three patients (183 women and 180 men) were treated with IFX since 2000. Mean age was 33.5 +/- 11.2 years and the mean duration of disease was 6.7 +/- 6.1 years. The population included 114 patients (31.4%) with therapy-refractory CD, 195 patients (53.7%) with fistulas, 16 patients (4.4%) with both therapy-refractory CD and fistulas, and 26 patients (7.2%) with steroid dependent CD. Five patients (1.4%) were treated with metastatic CD and 7 patients (1.9%) with other CD related indications. A full course of IFX induction therapy was successfully administered in 299 patients, and the overall response rate (CDAI decrease of 70 points) was 86.2% (313/363). A higher response rate was observed in younger patients and patients with shorter disease duration or colonic manifestations of CD. The response rate was lower in patients without concomitant immunosuppressant therapy compared to those with concomitant immunosuppressant therapy (73.0% vs. 88.2%, respectively; p<0.05). Higher response rate (closure of 50% or more of the fistulas) were observed in perianal fistulas compared to other forms. Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%), 17 delayed type hypersensitivity (4.7%), 16 infections (4.4%), and 3 malignancies (0.8%). CONCLUSIONS: IFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not influence the efficacy of IFX induction therapy.

• Evaluation of the combined application of ethanol-fixed and formaldehyde-fixed neutrophil substrates for identifying atypical P-ANCA in inflammatory bowel disease.

  Authors: Maria Papp, Istvan Altorjay, Gabriella Lakos, Judit Tumpek, Sandor Sipka, Tamas Dinya, Karoly Palatka, Gabor Veres, Miklos Udvardy, Peter Laszlo Lakatos

  Clinical and vaccine immunology : CVI. 02/2009;

  No clear guidelines for indirect immunofluorescence (IIF) detection and interpretation of antineutrophil cytoplasmic antibodies (ANCA) are proposed in inflammatory bowel diseases (IBD). We evaluatedNo clear guidelines for indirect immunofluorescence (IIF) detection and interpretation of antineutrophil cytoplasmic antibodies (ANCA) are proposed in inflammatory bowel diseases (IBD). We evaluated the reliability of combined use of ethanol- and formalin-fixed neutrophil substrates to identify atypical perinuclear (P)-ANCA under routine laboratory circumstances by indirect immunofluorescence. 204 IBD patients were assessed by four different fluorescence substrates in two distinct laboratories. Anti-myeloperoxidase (MPO) and anti-proteinase-3 (PR-3) and other specific granule proteins (elastase, lactoferrin, cathepsin G, lysozyme and bactericidal permeability-increasing protein [BPI]) were measured by ELISA. Combined application of ethanol- and formalin slides to detect atypical P-ANCA reflected lack of agreement between assays (kappa</=0.39) in the inter-assay and moderate agreement in the inter-observer study (kappa=0.42). After combining atypical and typical P-ANCA patterns together, the consensus greatly improved. 26.9% of patients were P-ANCA positive with at least 2 tests (UC: 44.3% and CD: 13.1%; p<0.0001), while overall ANCA positivity was 22.5%-34.8%. Combined application of ethanol-fixed and formaldehyde-fixed neutrophil substrates did not facilitate the differentiation between P-ANCA and atypical P-ANCA, and the results were not consistent when using substrates from different sources. Combining all P-ANCAs together ensures the highest sensitivity and specificity in differentiating UC from CD.

• Pancreatic autoantibodies are associated with reactivity to microbial antibodies, penetrating disease behavior, perianal disease, and extraintestinal manifestations, but not with NOD2/CARD15 or TLR4 genotype in a hungarian IBD cohort.

  Authors: Peter Laszlo Lakatos, Istvan Altorjay, Tamas Szamosi, Karoly Palatka, Zsuzsanna Vitalis, Judit Tumpek, Sandor Sipka, Miklos Udvardy, Tamas Dinya, Laszlo Lakatos, Agota Kovacs, Tamas Molnar, Zsolt Tulassay, Pal Miheller, Zsolt Barta, Winfried Stocker, Janos Papp, Gabor Veres, Maria Papp

  Inflammatory bowel diseases. 10/2008;

  Background: Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. ConventionalBackground: Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. Conventional antibodies and carbohydrates (glycans) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Our aim was to determine the accuracy of PAB and GAB autoantibodies as well as to study relevant phenotype-serotype associations.Methods: A Hungarian study cohort of 1092 subjects, including 689 well-characterized, unrelated IBD patients (CD: 579, m/f ratio: 274/305, duration: 7.9 +/- 11.2 years; UC: 110, m/f ratio: 53/57, duration: 8.9 +/- 9.8 years), 139 celiac patients, 100 healthy, and 64 non-IBD gastrointestinal controls were investigated. Sera were assayed for PAB-GAB IgA/IgG, anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCA), and anti-glycans. TLR4 and NOD2/CARD15 was tested by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined.Results: The prevalence of PAB was significantly more frequent in CD (41.1%) versus UC (22.7%), celiac (22.3%), and controls (8% and 4.6%, P < 0.01 for each), while GAB detection was poor in all groups except UC (15.4%). In CD the combination of PAB and/or anti-glycans/ASCA increased the sensitivity to 72% and 59%, respectively, for isolated colonic disease. PAB was associated to gylcans (odds ratio [OR] 1.74,P = 0.002), ASCA IgG/IgA (OR 1.75, P = 0.002), Omp (OR 1.86, P = 0.001) as well as perforating, perianal disease, arthritis, ocular, and cutaneous manifestations (P = 0.002-0.032). In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery. No associations were found in UC.Conclusions: PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.(Inflamm Bowel Dis 2008).

• New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort.

  Authors: Maria Papp, Istvan Altorjay, Nir Dotan, Karoly Palatka, Ildiko Foldi, Judit Tumpek, Sandor Sipka, Miklos Udvardy, Tamas Dinya, Laszlo Lakatos, Agota Kovacs, Tamas Molnar, Zsolt Tulassay, Pal Miheller, Gary L Norman, Tamas Szamosi, Janos Papp, Peter L Lakatos

  The American journal of gastroenterology. 04/2008; 103(3):665-81.

  BACKGROUND: Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importanceBACKGROUND: Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel diseases (IBD). Our aim was to determine whether a panel of new antibodies against bacterial proteins and carbohydrates could help differentiate among the various forms of IBD, and whether they were associated with particular clinical manifestations in a Hungarian cohort of IBD patients. METHODS: Six hundred fifty-two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease] 557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95, men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the patients' medical charts. RESULTS: Sixty-six percent of the CD patients had at least one of the investigated antibodies. Among glycan antibodies, gASCA or the combination of gASCA and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) was most accurate for differentiating between CD and UC. ASCA and gASCA assays performed similarly. Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA, and OmpC were associated with more complicated disease behavior (P < 0.0001) and need for surgery in CD (P= 0.023). A serological dosage effect was also observed. gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene-dosage effect. No serotype-phenotype associations were found in UC. CONCLUSIONS: Antibody response to this new panel of serological markers was associated with complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in this eastern European IBD cohort.

• Seroreactivity to microbial components in Crohn's disease is associated with ileal involvement, noninflammatory disease behavior and NOD2/CARD15 genotype, but not with risk for surgery in a Hungarian cohort of IBD patients.

  Authors: Maria Papp, Istvan Altorjay, Gary L Norman, Zakera Shums, Karoly Palatka, Zsuzsanna Vitalis, Ildiko Foldi, Gabriella Lakos, Judit Tumpek, Miklos L Udvardy [......] Simon Fischer, Laszlo Lakatos, Agota Kovacs, Laszlo Bene, Tamas Molnar, Zsolt Tulassay, Pal Miheller, Gabor Veres, Janos Papp, Peter Laszlo Lakatos

  Inflammatory bowel diseases. 09/2007; 13(8):984-92.

  BACKGROUND: Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to beBACKGROUND: Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients. METHODS: In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC. CONCLUSIONS: Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.

• Haptoglobin polymorphisms are associated with Crohn's disease, disease behavior, and extraintestinal manifestations in Hungarian patients.

  Authors: Maria Papp, Peter Laszlo Lakatos, Karoly Palatka, Ildiko Foldi, Miklos Udvardy, Jolan Harsfalvi, Istvan Tornai, Zsuzsanna Vitalis, Tamas Dinya, Agota Kovacs, Tamas Molnar, Pal Demeter, Janos Papp, Laszlo Lakatos, Istvan Altorjay

  Digestive diseases and sciences. 06/2007; 52(5):1279-84.

  Functional differences and association with inflammatory disorders were found relating to three major haptoglobin (Hp) phenotypes. Our aim was to investigate Hp polymorphisms in Hungarian patientsFunctional differences and association with inflammatory disorders were found relating to three major haptoglobin (Hp) phenotypes. Our aim was to investigate Hp polymorphisms in Hungarian patients with Crohn's disease (CD). Four hundred sixty-eight CD patients and 384 healthy controls were examined. Hp phenotypes were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of the sera. The frequency of the Hp(1) allele was significantly higher in CD (0.395; OR, 1.24; 95% CI, 1.02-1.52; P=0.03) compared to controls (0.345). In CD, Hp phenotype was associated with disease behavior (OR [Hp(2-1) vs other], 2.06; 95% CI, 1.29-3.28 for inflammatory behavior). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in the Hp 2-2 compared to the Hp 1-1 phenotype (6.5% vs. 0.0%; P=0.039). We conclude that the Hp polymorphism is associated with CD, inflammatory disease behavior, and primary sclerosing cholangitis in Hungarian patients. Further studies are required to evaluate the significance of Hp polymorphisms in other populations from geographically diverse regions.

• DLG5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease.

  Authors: Peter Laszlo Lakatos, Simon Fischer, Karolien Claes, Agota Kovacs, Tamas Molnar, Istvan Altorjay, Pal Demeter, Zsolt Tulassay, Karoly Palatka, Maria Papp, Paul Rutgeerts, Ferenc Szalay, Janos Papp, Severine Vermeire, Laszlo Lakatos

  Inflammatory bowel diseases. 06/2006; 12(5):362-8.

  BACKGROUND: Recent data suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographicalBACKGROUND: Recent data suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5 R30Q variant in Hungarian IBD patients. MATERIALS AND METHODS: We investigated 773 unrelated IBD patients (age 38.1 +/- 10.3 years; duration, 8.8 +/- 7.5 years; Crohn's disease [CD]: 639; male/female, 309/330; duration, 8.4 +/- 7.1 years; ulcerative colitis [UC]: 134; male/female, 63/71; duration, 10.6 +/- 8.9 years) and 150 healthy subjects. DLG5 R30Q and TLR4 D299G variants were tested by polymerase chain reaction/restriction fragment length polymorphism. DNA was screened for NOD2/CARD15 mutations by denaturing high-performance liquid chromatography. Detailed clinical phenotype was determined by reviewing the medical charts. RESULTS: The frequency of the R30Q variant allele was not significantly different in IBD (22.0%), CD (20.8%), and UC (27.6%) patients compared with healthy control subjects (28.0%). In CD, the 113A variant allele was associated with steroid resistance (16.3% vs noncarriers, 7.6%; odds ratio [OR], 2.4; 95% CI 1.3-4.5; P = 0.013). In a logistic regression model carriage of DLG5 R30Q, perianal involvement and frequent relapses were independently associated with steroid resistance. No phenotype-genotype associations were found in UC patients, although a trend toward more extensive disease was observed in carriers of the variant allele (OR = 2.1; 95% CI 0.95-4.4; P = 0.07). CONCLUSIONS: The present data strongly contrast previous data from Germany. DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids. Further studies are required to evaluate the significance of DLG5 in other populations from geographically diverse regions.

• THE ASSOCIATION OF REDUCED ENDOTHELIUM DERIVED RELAXING FACTOR-NO PRODUCTION WITH ENDOTHELIAL DAMAGE AND INCREASED IN VIVO PLATELET ACTIVATION IN PATIENTS WITH DIABETES MELLITUS

  Authors: Marianna Huszka, Miklos Kaplar, Laszlo Rejto, Istvan Tornai, Karoly Palatka, Pal Laszlo, Miklos Udvardy

  Thrombosis Research.

  The role of reduced endothelial production of EDRF-NO in the pathogenesis of diabetic angiopathy has received much attention, however, most of the rather conflicting data were gained from animalThe role of reduced endothelial production of EDRF-NO in the pathogenesis of diabetic angiopathy has received much attention, however, most of the rather conflicting data were gained from animal experiments. Limited human experience seems to be available in insulin dependent diabetes, calling attention to decreased EDRF-NO production. Hereby the clinical, as well as laboratory investigation (urinary and serum nitrate/nitrite, lipid peroxidation, glucometabolic parameters, endothelial and in vivo platelet activation markers, etc.) of 35 non-insulin dependent (NIDDM) and 15 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were proven to be reduced in both patients groups. This change was independent of diabetes duration, presence of macroangiopathy, coronary heart disease and the glucometabolic parameters, however, correlation was registered with lipid peroxidation (total antioxidant status). An inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented in NIDDM, this correlation was much stronger in IDDM. Moreover, in IDDM patients reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta-thromboglobulin levels. The data presented here support to the hypothesis, that EDRF-NO production is reduced in diabetes and this reduction seems to correlate with endothelial damage. In IDDM the decreased nitrate/nitrite excretion may also lead to increased in vivo platelet activation, which suggests that the reduced amount of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM. © 1997 Elsevier Science Ltd