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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318281f2d3
Original Clinical Articles

Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease

Zhulina, Yaroslava MD*,†; Hahn-Strömberg, Victoria PhD‡,§; Shamikh, Alia MD‡,§; Peterson, Christer G. B. PhD; Gustavsson, Anders MD*,†; Nyhlin, Nils MD, PhD*; Wickbom, Anna MD*,†; Bohr, Johan MD, PhD*,†; Bodin, Lennart PhD; Tysk, Curt MD, PhD*,†; Carlson, Marie MD, PhD**; Halfvarson, Jonas MD, PhD*,†

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Abstract

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-κB) 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-κB 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-κB 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-κB, 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.

Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

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