title: Subclinical inflammation with increased neutrophil activity in healthy twin siblings reflect environmental influence in the pathogenesis of inflammatory bowel disease.
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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
authors.forename: Yaroslava
authors.initials: Y
authors.lastname: Zhulina
authors.forename: Victoria
authors.initials: V
authors.lastname: Hahn-Strömberg
authors.forename: Alia
authors.initials: A
authors.lastname: Shamikh
authors.forename: Christer G B
authors.initials: CG
authors.lastname: Peterson
authors.forename: Anders
authors.initials: A
authors.lastname: Gustavsson
authors.forename: Nils
authors.initials: N
authors.lastname: Nyhlin
authors.forename: Anna
authors.initials: A
authors.lastname: Wickbom
authors.forename: Johan
authors.initials: J
authors.lastname: Bohr
authors.forename: Lennart
authors.initials: L
authors.lastname: Bodin
authors.forename: Curt
authors.initials: C
authors.lastname: Tysk
authors.forename: Marie
authors.initials: M
authors.lastname: Carlson
authors.forename: Jonas
authors.initials: J
authors.lastname: Halfvarson
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004200:Diseases in Twins / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004781:Environmental Exposure / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D011379:Prognosis; D035781:Siblings; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055815:Young Adult
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D016328:NF-kappa B; D009195:Peroxidase