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Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Orebro University Hospital. Department of Internal Medicine, Division of Gastroenterology.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Pathology, Örebro University Hospital, Örebro; Department of Clinical Medicine, Örebro University, Örebro.
Department of Pathology, Örebro University Hospital, Örebro; Department of Clinical Medicine, Örebro University, Örebro.
Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala.
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2013 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 8, 1725-1731 p.Article in journal (Refereed) Published
Abstract [en]

Background: The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.

Methods: Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.

Results: In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.

Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.

Place, publisher, year, edition, pages
Philadelphia, USA: Lippincott Williams & Wilkins, 2013. Vol. 19, no 8, 1725-1731 p.
Keyword [en]
Inflammatory bowel disease, twins, genetics, subclinical activity, nuclear factor-kappa B, myeloperoxidase, F-calprotectin
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-33716DOI: 10.1097/MIB.0b013e318281f2d3ISI: 000329363800019PubMedID: 23669399Scopus ID: 2-s2.0-84884574092OAI: oai:DiVA.org:oru-33716DiVA: diva2:695868
Funder
Swedish Research Council
Note

Funding Agencies:

Bengt Ihre's foundation  

Nanna Svartz' foundation  

Orebro University Hospital Research Foundation  

Orebro County Research Foundation  

Swedish Foundation for Gastrointestinal research

Available from: 2014-02-12 Created: 2014-02-12 Last updated: 2017-03-23Bibliographically approved
In thesis
1. Chrohn's disease: aspects of epidemiology, clinical course, and faecal calprotectin
Open this publication in new window or tab >>Chrohn's disease: aspects of epidemiology, clinical course, and faecal calprotectin
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The overall aim of this thesis was to study epidemiological and clinical changes in the natural history of Crohn’s disease, its phenotype, the need for surgery and pharmacological therapy over time, as well as the role of faecal calprotectin as a biomarker of pathophysiology and disease course.

An increased incidence and prevalence of Crohn’s disease was seen in the period 1963-2010. The proportion of patients with non-stricturing, non-penetrating disease behaviour at diagnosis increased, suggesting that either patients with Crohn’s disease are diagnosed earlier in their disease course today or that the Crohn’s disease phenotype is changing.

A decrease in complicated disease behaviour, an increased use of immunomodulators, and a reduced frequency of surgical procedures five years after Crohn’s diagnosis was observed. The decrease in surgery at five years seemed to be explained mainly by a decrease in early surgery within three months from diagnosis, likely reflecting an increased proportion of patients with non-stricturing, non-penetrating disease. This suggests that the introduction of new treatment alternatives alone does not explain the reduction in surgery rates, and an increasing proportion of patients with uncomplicated disease at diagnosis may also play an important role.

Subclinical mucosal inflammation, mirrored by increased NFkB activity and increased neutrophil activity (i.e. FC and MPO expression), was observed in healthy twin siblings in both discordant monozygotic and discordant dizygotic twin pairs with IBD. These findings strongly support the hypothesis of an ongoing subclinical mucosal inflammation at the molecular level in healthy first-degree relatives of IBD patients.

Baseline FC as well as consecutive FC measurements predict relapse in IBD. The doubling of FC value increased the risk of relapse by 101% in the following three months. This increased risk attenuates with time by 20% for every three month period since the sample was obtained.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2016. 97 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 141
Keyword
Crohn’s disease, epidemiology, faecal calprotectin
National Category
Family Medicine Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-49436 (URN)978-91-7529-135-2 (ISBN)
Public defence
2016-06-02, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
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Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2016-05-17Bibliographically approved

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Zhulina, YaroslavaHahn-Strömberg, VictoriaGustavsson, AndersNyhlin, NilsWickbom, AnnaBohr, JohanBodin, LennartTysk, CurtHalfvarson, Jonas
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