Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
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
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.
Inflammatory bowel disease, twins, genetics, subclinical activity, nuclear factor-kappa B, myeloperoxidase, F-calprotectin
Medical and Health Sciences Gastroenterology and Hepatology
Research subject Medicine
IdentifiersURN: urn:nbn:se:oru:diva-33716DOI: 10.1097/MIB.0b013e318281f2d3ISI: 000329363800019PubMedID: 23669399ScopusID: 2-s2.0-84884574092OAI: oai:DiVA.org:oru-33716DiVA: diva2:695868
FunderSwedish Research Council
Bengt Ihre's foundation
Nanna Svartz' foundation
Orebro University Hospital Research Foundation
Orebro County Research Foundation
Swedish Foundation for Gastrointestinal research2014-02-122014-02-122016-05-16Bibliographically approved