Maria Papp1, Nora Sipeki1, Tamas Tornai1, Istvan Altorjay1, Gary L Norman2, Zakera Shums2, Dirk Roggenbuck3, Kai Fechner4, Winfried Stöcker4, Peter Antal-Szalmas5, Gabor Veres6, Peter Laszlo Lakatos6. 1. Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 2. Inova Diagnostics, San Diego, CA, USA. 3. Faculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany GA Generic Assays GmbH, Dahlewitz, Germany. 4. Institute of Experimental Immunology, Euroimmun AG, Luebeck, Germany. 5. Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 6. 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Abstract
BACKGROUNDS: Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort. METHODS: Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months]. RESULTS: Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001). CONCLUSIONS: The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD.
BACKGROUNDS: Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CDpatient cohort. METHODS: Sera of 458 consecutive well-characterised IBDpatients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months]. RESULTS: Totals of 12.4% and 20.8% of CDpatients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001). CONCLUSIONS: The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD.
Authors: Tamas Tornai; David Tornai; Nora Sipeki; Istvan Tornai; Rayan Alsulaimani; Kai Fechner; Dirk Roggenbuck; Gary L Norman; Gabor Veres; Gabriella Par; Alajos Par; Ferenc Szalay; Peter Laszlo Lakatos; Peter Antal-Szalmas; Maria Papp Journal: Sci Rep Date: 2018-01-10 Impact factor: 4.379
Authors: Tamas Tornai; Eszter Palyu; Zsuzsanna Vitalis; Istvan Tornai; David Tornai; Peter Antal-Szalmas; Gary L Norman; Zakera Shums; Gabor Veres; Antal Dezsofi; Gabriella Par; Alajos Par; Peter Orosz; Ferenc Szalay; Peter Laszlo Lakatos; Maria Papp Journal: World J Gastroenterol Date: 2017-08-07 Impact factor: 5.742
Authors: Gyorgy Kovacs; Nora Sipeki; Boglarka Suga; Tamas Tornai; Kai Fechner; Gary L Norman; Zakera Shums; Peter Antal-Szalmas; Maria Papp Journal: PLoS One Date: 2018-03-28 Impact factor: 3.240
Authors: Michael P Horn; Anna Maria Peter; Franziska Righini Grunder; Alexander B Leichtle; Johannes Spalinger; Susanne Schibli; Christiane Sokollik Journal: PLoS One Date: 2018-12-17 Impact factor: 3.240
Authors: Mandy Sowa; Rafał Kolenda; Daniel C Baumgart; Johann Pratschke; Maria Papp; Tamas Tornai; Jaroslaw Suchanski; Dimitrios P Bogdanos; Maria G Mytilinaiou; Jutta Hammermann; Martin W Laass; Karsten Conrad; Christoph Schramm; Andre Franke; Dirk Roggenbuck; Peter Schierack Journal: Front Immunol Date: 2018-08-28 Impact factor: 7.561