Skip to main content
Top
Published in: Digestive Diseases and Sciences 2/2023

Open Access 22-08-2022 | Ulcerative Colitis | Original Article

Anti-Saccharomyces cerevisiae Antibodies Are Only Modestly More Common in Subjects Later Developing Crohn's Disease

Authors: L. Bodecker-Zingmark, L. Widbom, J. Hultdin, C. Eriksson, P. Karling

Published in: Digestive Diseases and Sciences | Issue 2/2023

Login to get access

Abstract

Background

The pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.

Aims

To study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.

Methods

Antibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.

Results

The mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.

Conclusions

We found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.
Literature
1.
go back to reference Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1–s106.CrossRef Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1–s106.CrossRef
2.
go back to reference Busch K, Ludvigsson JF, Ekstrom-Smedby K, Ekbom A, Askling J, Neovius M. Nationwide prevalence of inflammatory bowel disease in Sweden: a population-based register study. Aliment Pharmacol Ther. 2014;39:57–68.CrossRef Busch K, Ludvigsson JF, Ekstrom-Smedby K, Ekbom A, Askling J, Neovius M. Nationwide prevalence of inflammatory bowel disease in Sweden: a population-based register study. Aliment Pharmacol Ther. 2014;39:57–68.CrossRef
3.
go back to reference Chang JT. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med. 2020;383:2652–2664.CrossRef Chang JT. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med. 2020;383:2652–2664.CrossRef
4.
go back to reference Sendid B, Colombel JF, Jacquinot PM, Faille C, Fruit J, Cortot A et al. Specific antibody response to oligomannosidic epitopes in Crohn’s disease. Clin Diagn Lab Immun. 1996;3:219–226.CrossRef Sendid B, Colombel JF, Jacquinot PM, Faille C, Fruit J, Cortot A et al. Specific antibody response to oligomannosidic epitopes in Crohn’s disease. Clin Diagn Lab Immun. 1996;3:219–226.CrossRef
5.
go back to reference Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut. 1998;42:788–791.CrossRef Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut. 1998;42:788–791.CrossRef
6.
go back to reference Walker LJ, Aldhous MC, Drummond HE, Smith BRK, Nimmo ER, Arnott IDR et al. Anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn’s disease are associated with disease severity but not NOD2/CARD15 mutations. Clin Exp Immunol. 2004;135:490–496.CrossRef Walker LJ, Aldhous MC, Drummond HE, Smith BRK, Nimmo ER, Arnott IDR et al. Anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn’s disease are associated with disease severity but not NOD2/CARD15 mutations. Clin Exp Immunol. 2004;135:490–496.CrossRef
7.
go back to reference Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2012;18:1340–1355.CrossRef Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2012;18:1340–1355.CrossRef
8.
go back to reference Peen E, Almer S, Bodemar G, Ryden BO, Sjolin C, Tejle K et al. Anti-Lactoferrin Antibodies and Other Types of Anca in Ulcerative-Colitis, Primary Sclerosing Cholangitis, and Crohns-Disease. Gut. 1993;34:56–62.CrossRef Peen E, Almer S, Bodemar G, Ryden BO, Sjolin C, Tejle K et al. Anti-Lactoferrin Antibodies and Other Types of Anca in Ulcerative-Colitis, Primary Sclerosing Cholangitis, and Crohns-Disease. Gut. 1993;34:56–62.CrossRef
9.
go back to reference Papp M, Altorjay I, Dotan N, Palatka K, Foldi I, Tumpek J et al. 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. American Journal of Gastroenterology. 2008;103:665–681.CrossRef Papp M, Altorjay I, Dotan N, Palatka K, Foldi I, Tumpek J et al. 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. American Journal of Gastroenterology. 2008;103:665–681.CrossRef
10.
go back to reference Homsak E, Micetic-Turk D, Bozic B. Autoantibodies pANCA, GAB and PAB in inflammatory bowel disease: prevalence, characteristics and diagnostic value. Wien Klin Wochenschr. 2010;122:19–25.CrossRef Homsak E, Micetic-Turk D, Bozic B. Autoantibodies pANCA, GAB and PAB in inflammatory bowel disease: prevalence, characteristics and diagnostic value. Wien Klin Wochenschr. 2010;122:19–25.CrossRef
11.
go back to reference Kovacs M, Lakatos PL, Papp M, Jacobsen S, Nemes E, Polgar M et al. Pancreatic Autoantibodies and Autoantibodies Against Goblet Cells in Pediatric Patients With Inflammatory Bowel Disease. J Pediatr Gastr Nutr. 2012;55:429–435.CrossRef Kovacs M, Lakatos PL, Papp M, Jacobsen S, Nemes E, Polgar M et al. Pancreatic Autoantibodies and Autoantibodies Against Goblet Cells in Pediatric Patients With Inflammatory Bowel Disease. J Pediatr Gastr Nutr. 2012;55:429–435.CrossRef
12.
go back to reference Lawrance IC, Hall A, Leong R, Pearce C, Murray K. A comparative study of goblet cell and pancreatic exocine autoantibodies combined with ASCA and pANCA in Chinese and Caucasian patients with IBD. Inflammatory Bowel Diseases. 2005;11:890–897.CrossRef Lawrance IC, Hall A, Leong R, Pearce C, Murray K. A comparative study of goblet cell and pancreatic exocine autoantibodies combined with ASCA and pANCA in Chinese and Caucasian patients with IBD. Inflammatory Bowel Diseases. 2005;11:890–897.CrossRef
13.
go back to reference Joossens S, Vermeire S, Van Steen K, Godefridis G, Claessens G, Pierik M et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflammatory Bowel Diseases. 2004;10:771–777.CrossRef Joossens S, Vermeire S, Van Steen K, Godefridis G, Claessens G, Pierik M et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflammatory Bowel Diseases. 2004;10:771–777.CrossRef
14.
go back to reference Papp M, Sipeki N, Tornai T, Altorjay I, Norman GL, Shums Z et al. Rediscovery of the Anti-Pancreatic Antibodies and Evaluation of their Prognostic Value in a Prospective Clinical Cohort of Crohn’s Patients: The Importance of Specific Target Antigens [GP2 and CUZD1]. J Crohns Colitis. 2015;9:659–668.CrossRef Papp M, Sipeki N, Tornai T, Altorjay I, Norman GL, Shums Z et al. Rediscovery of the Anti-Pancreatic Antibodies and Evaluation of their Prognostic Value in a Prospective Clinical Cohort of Crohn’s Patients: The Importance of Specific Target Antigens [GP2 and CUZD1]. J Crohns Colitis. 2015;9:659–668.CrossRef
15.
go back to reference Hoie O, Aamodt G, Vermeire S, Bernklev T, Odes S, Wolters FL, et al. Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years. Journal of Crohns & Colitis. 2008;2:114–22. Hoie O, Aamodt G, Vermeire S, Bernklev T, Odes S, Wolters FL, et al. Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years. Journal of Crohns & Colitis. 2008;2:114–22.
16.
go back to reference Choung RS, Princen F, Stockfisch TP, Torres J, Maue AC, Porter CK et al. Serologic microbial associated markers can predict Crohn’s disease behaviour years before disease diagnosis. Aliment Pharmacol Ther. 2016;43:1300–1310.CrossRef Choung RS, Princen F, Stockfisch TP, Torres J, Maue AC, Porter CK et al. Serologic microbial associated markers can predict Crohn’s disease behaviour years before disease diagnosis. Aliment Pharmacol Ther. 2016;43:1300–1310.CrossRef
17.
go back to reference Ferrante M, Henckaerts L, Joossens M, Pierik M, Joossens S, Dotan N et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56:1394–1403.CrossRef Ferrante M, Henckaerts L, Joossens M, Pierik M, Joossens S, Dotan N et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56:1394–1403.CrossRef
18.
go back to reference Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005;54:1232–1236.CrossRef Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005;54:1232–1236.CrossRef
19.
go back to reference van Schaik FD, Oldenburg B, Hart AR, Siersema PD, Lindgren S, Grip O et al. Serological markers predict inflammatory bowel disease years before the diagnosis. Gut. 2013;62:683–688.CrossRef van Schaik FD, Oldenburg B, Hart AR, Siersema PD, Lindgren S, Grip O et al. Serological markers predict inflammatory bowel disease years before the diagnosis. Gut. 2013;62:683–688.CrossRef
20.
go back to reference Torres J, Petralia F, Sato T, Wang P, Telesco SE, Choung RS et al. Serum Biomarkers Identify Patients Who Will Develop Inflammatory Bowel Diseases Up to 5 Years Before Diagnosis. Gastroenterology. 2020;159:96–104.CrossRef Torres J, Petralia F, Sato T, Wang P, Telesco SE, Choung RS et al. Serum Biomarkers Identify Patients Who Will Develop Inflammatory Bowel Diseases Up to 5 Years Before Diagnosis. Gastroenterology. 2020;159:96–104.CrossRef
21.
go back to reference Norberg M, Wall S, Boman K, Weinehall L. The Vasterbotten Intervention Programme: background, design and implications. Global Health Action. 2010;3. Norberg M, Wall S, Boman K, Weinehall L. The Vasterbotten Intervention Programme: background, design and implications. Global Health Action. 2010;3.
22.
go back to reference Rantapaa-Dahlqvist S, de Jong BAW, Berglin E, Hallmans G, Wadell G, Stenlund H et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48:2741–2749.CrossRef Rantapaa-Dahlqvist S, de Jong BAW, Berglin E, Hallmans G, Wadell G, Stenlund H et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48:2741–2749.CrossRef
23.
go back to reference Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–753.CrossRef Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–753.CrossRef
24.
go back to reference Widbom L, Ekblom K, Karling P, Hultdin J. Patients developing inflammatory bowel disease have iron deficiency and lower plasma ferritin years before diagnosis: a nested case-control study. Eur J Gastroen Hepat. 2020;32:1147–1153.CrossRef Widbom L, Ekblom K, Karling P, Hultdin J. Patients developing inflammatory bowel disease have iron deficiency and lower plasma ferritin years before diagnosis: a nested case-control study. Eur J Gastroen Hepat. 2020;32:1147–1153.CrossRef
25.
go back to reference Lundgren D, Widbom L, Hultdin J, Karling P. Preclinical Markers in Inflammatory Bowel Disease. A Nested Case-Control Study. Crohns Colitis 360. 2021 Oct;3(4). Lundgren D, Widbom L, Hultdin J, Karling P. Preclinical Markers in Inflammatory Bowel Disease. A Nested Case-Control Study. Crohns Colitis 360. 2021 Oct;3(4).
26.
go back to reference Vermeire S, Peeters M, Vlietinck R, Joossens S, Den Hond E, Bulteel V et al. Anti-Saccharomyces cerevisiae antibodies (ASCA), phenotypes of IBD, and intestinal permeability: A study in IBD families. Inflammatory Bowel Diseases. 2001;7:8–15.CrossRef Vermeire S, Peeters M, Vlietinck R, Joossens S, Den Hond E, Bulteel V et al. Anti-Saccharomyces cerevisiae antibodies (ASCA), phenotypes of IBD, and intestinal permeability: A study in IBD families. Inflammatory Bowel Diseases. 2001;7:8–15.CrossRef
27.
go back to reference Annese V, Andreoli A, Andriulli A, D’Inca R, Gionchetti P, Latiano A et al. Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in Crohn’s disease and ulcerative colitis: A GISC study. American Journal of Gastroenterology. 2001;96:2407–2412.CrossRef Annese V, Andreoli A, Andriulli A, D’Inca R, Gionchetti P, Latiano A et al. Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in Crohn’s disease and ulcerative colitis: A GISC study. American Journal of Gastroenterology. 2001;96:2407–2412.CrossRef
28.
go back to reference Seibold F, Stich O, Hufnagl R, Kamil S, Scheurlen M. Anti-Saccharomyces cerevisiae antibodies in inflammatory bowel disease: a family study. Scand J Gastroentero. 2001;36:196–201.CrossRef Seibold F, Stich O, Hufnagl R, Kamil S, Scheurlen M. Anti-Saccharomyces cerevisiae antibodies in inflammatory bowel disease: a family study. Scand J Gastroentero. 2001;36:196–201.CrossRef
29.
go back to reference Hallen-Adams HE, Suhr MJ. Fungi in the healthy human gastrointestinal tract. Virulence. 2017;8:352–358.CrossRef Hallen-Adams HE, Suhr MJ. Fungi in the healthy human gastrointestinal tract. Virulence. 2017;8:352–358.CrossRef
30.
go back to reference Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: A comprehensive review. Clin Infect Dis. 2005;41:1559–1568.CrossRef Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: A comprehensive review. Clin Infect Dis. 2005;41:1559–1568.CrossRef
31.
go back to reference Mallant-Hent RC, Mooij M, von Blomberg BME, Linskens RK, van Bodegrave AA, Savelkoul PHM. Correlation between Saccharomyces cerevisiae DNA in intestinal mucosal samples and anti-Saccharomyces cerevisiae antibodies in serum of patients with IBD. World J Gastroentero. 2006;12:292–297.CrossRef Mallant-Hent RC, Mooij M, von Blomberg BME, Linskens RK, van Bodegrave AA, Savelkoul PHM. Correlation between Saccharomyces cerevisiae DNA in intestinal mucosal samples and anti-Saccharomyces cerevisiae antibodies in serum of patients with IBD. World J Gastroentero. 2006;12:292–297.CrossRef
32.
go back to reference Pavlidis P, Shums Z, Koutsoumpas AL, Milo J, Papp M, Umemura T et al. Diagnostic and clinical significance of Crohn’s disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA. Clin Chim Acta. 2015;20:176–181.CrossRef Pavlidis P, Shums Z, Koutsoumpas AL, Milo J, Papp M, Umemura T et al. Diagnostic and clinical significance of Crohn’s disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA. Clin Chim Acta. 2015;20:176–181.CrossRef
Metadata
Title
Anti-Saccharomyces cerevisiae Antibodies Are Only Modestly More Common in Subjects Later Developing Crohn's Disease
Authors
L. Bodecker-Zingmark
L. Widbom
J. Hultdin
C. Eriksson
P. Karling
Publication date
22-08-2022
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2023
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-022-07630-5

Other articles of this Issue 2/2023

Digestive Diseases and Sciences 2/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine