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  • 1.
    Amcoff, Karin
    Örebro University, School of Medical Sciences.
    Serological and faecal biomarkers in inflammatory bowel disease2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are relapsing and remitting disorders characterised by chronic inflammation at various sites in the gastrointestinal tract, resulting in diarrhoea and abdominal pain. Neither the aetiology nor the pathophysiology is yet fully understood, and there is currently no cure.

    The overall aim of this thesis was to add a piece of the puzzle to understanding the complex pathogenesis of IBD; to determine the role of genetic and environmental factors in the development of antibodies in IBD - which could provide insight to the aetiology of the diseases; and to find sensitive and specific faecal biomarkers to predict future flare in the diseases.

    By conducting twin-studies, we found that some serological antibodies associated with Crohn's disease seemed to be genetically predisposed (anti-OmpC and anti-I2). Genetic predisposition do not play a predominant role in the generation of other antibodies, such as ASCA, anti-CBir1 or the autoantibody most commonly found in ulcerative colitis; pANCA. Exposure to environmental factors during childhood are suggested to be of importance in the development of ASCA and anti-CBir1 in CD. Active smoking seemed to have a protective effect against development of pANCA.

    Faecal calprotectin is a known marker for intestinal inflammation. In our third study, three faecal calprotectin assays were compared, which revealed overall poor agreement. This implies that standardisation of the method is highly needed.

    In our final study, we measured faecal eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in patients with IBD every third month over a two-year period. The results revealed that the risk of relapse in UC can be predicted by measuring EDN consecutively.

    List of papers
    1. Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease
    Open this publication in new window or tab >>Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease
    Show others...
    2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed) Published
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

    Place, publisher, year, edition, pages
    Oxford, United Kingdom: Oxford University Press, 2016
    Keywords
    Crohn’s disease, serology, genetics
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-50589 (URN)10.1093/ecco-jcc/jjw021 (DOI)000377920100010 ()26818662 (PubMedID)
    Available from: 2016-06-08 Created: 2016-06-08 Last updated: 2018-07-13Bibliographically approved
    2. Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin study
    Open this publication in new window or tab >>Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-64027 (URN)
    Available from: 2018-01-11 Created: 2018-01-11 Last updated: 2018-01-11Bibliographically approved
    3. Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
    Open this publication in new window or tab >>Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
    Show others...
    2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed) Published
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.

    Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).

    Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.

    Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

    Place, publisher, year, edition, pages
    Oxon, United Kingdom: Taylor & Francis, 2017
    Keywords
    Biomarker, Crohn's disease, faecal calprotectin, inflammatory bowel, disease, ulcerative colitis
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-53665 (URN)10.1080/00365521.2016.1256424 (DOI)000392488800015 ()27881032 (PubMedID)2-s2.0-84996799488 (Scopus ID)
    Funder
    Swedish Research Council, 521-2011-2764
    Note

    Funding Agencies:

    Örebro University Hospital Research Foundation OLL-333321

    Uppsala-Örebro Regional Research Foundation RFR-314671

    Available from: 2016-11-28 Created: 2016-11-28 Last updated: 2018-11-29Bibliographically approved
    4. Prognostic significance of eosinophile granule proteins in inflammatory bowel disease
    Open this publication in new window or tab >>Prognostic significance of eosinophile granule proteins in inflammatory bowel disease
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-64028 (URN)
    Available from: 2018-01-11 Created: 2018-01-11 Last updated: 2018-01-11Bibliographically approved
  • 2.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Bergenmalm, Daniel
    University Hospital Maastricht, Maastricht, The Netherlands.
    Pierik, Marie J.
    University Hospital Maastricht, Maastricht, The Netherlands.
    Colombel, Jean-Frederic
    University Hospital Gasthuisberg, Leuven, Belgium.
    Vermeire, Severine
    Karolinska Institute, Stockholm, Sweden.
    Bodin, Lennart
    Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin studyManuscript (preprint) (Other academic)
  • 3.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Zhulina, Yaroslava
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Lampinen, M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S181-S182Article in journal (Other academic)
  • 4.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Karolinska Institutet, Stockholm, Sweden.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, Marie
    Uppsala University, Uppsala, Sweden.
    Prognostic significance of eosinophile granule proteins in inflammatory bowel diseaseManuscript (preprint) (Other academic)
  • 5.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Marie
    Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit, Leuven,Belgium; VIB Center for the Biology of Disease, Leuven, Belgium; Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit, Brussels, Belgium.
    Pierik, Marie J.
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Jonkers, Daisy
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Bohr, Johan
    Örebro University, School of Health Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Sofie
    Gastroenterology, Catholic University of Leuven (KUL), Leuven, Belgium.
    Romberg-Camps, Mariëlle
    Department of Gastroenterology-Hepatology, Zuyderland Medical Center, Sittard, Netherlands.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Rutgeerts, Paul J.
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Tysk, Curt
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Colombel, Jean-Frederic
    Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA.
    Vermeire, Severine
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed)
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

  • 6.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Örebro University Hospital, Örebro, sweden.
    Stridsberg, Mats
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Lampinen, Maria
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Magnuson, Anders
    linical EpiSchool of Medical Sciences, Örebro University, Örebro, Sweden.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.

    Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).

    Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.

    Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

  • 7.
    Zhulina, Y.
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cao, Y.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Amcoff, Karin
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Carlson, M.
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Tysk, C.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    The prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel disease2016In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 44, no 5, p. 495-504Article in journal (Refereed)
    Abstract [en]

    Background: Faecal calprotectin, an established biomarker used to assess mucosal inflammation, has been shown to correlate with endoscopic activity in inflammatory bowel disease (IBD). Longitudinal monitoring of faecal calprotectin, however, has rarely been employed beyond assessment of therapy response and post hoc analyses of clinical trials.

    Aim: To study whether consecutive measurements of faecal calprotectin every third month are useful for monitoring patients with IBD in clinical remission.

    Methods: Patients aged 18 years or older, with a known diagnosis of IBD in clinical remission, were prospectively studied. Patients provided faecal samples every third month and were prospectively followed until the first clinical relapse or the end of the 2-year follow-up period. Measurements (EK-CAL, Bühlmann Lab. AG, Switzerland) were done at the end of the study. A Cox model with time-dependent covariates was used for analysis.

    Results: Among 104 patients, Crohn's disease (n = 49) and ulcerative colitis (n = 55), 37 had a relapse. A doubling of faecal calprotectin level between two consecutively collected samples was associated with a 101% increased risk of relapse (HR: 2.01; 95% CI: 1.53-2.65; P < 0.001). The relative risk of relapse attenuated with time (HR: 0.80; 95% CI: 0.75-0.86; P < 0.001), by a 20% decrease in risk of relapse per 3-month period since the sample was obtained.

    Conclusions: By consecutively measuring faecal calprotectin every third month, we quantified the risk of relapse related to faecal calprotectin change and observed attenuation of the risk across time. Our data suggest that longitudinal monitoring of faecal calprotectin is informative in predicting relapse in IBD.

  • 8.
    Zhulina, Yaroslava
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cao, Yang
    School of Medical Sciences, Örebro University, Örebro, Sweden; Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Amcoff, Karin
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Carlson, M.
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Faecal calprotectin for the prediction of relapse in inactive inflammatory bowel disease: - authors' reply2016In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 44, no 7, p. 770-771Article in journal (Refereed)
  • 9.
    Zhulina, Yaroslava
    et al.
    Örebro University, School of Health Sciences. Department of Gastroenterology.
    Cao, Yang
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Amcoff, Karin
    Örebro University, School of Health Sciences. Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Carlsson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel diseaseManuscript (preprint) (Other academic)
1 - 9 of 9
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