Genetic and shared environmental risk factors do not lead to eosinophil activation in healthy twins of IBD patients

Scand J Gastroenterol. 2020 Oct;55(10):1163-1170. doi: 10.1080/00365521.2020.1804994. Epub 2020 Aug 20.

Abstract

Objective: To examine the role of eosinophils in the pre-diagnostic phase of inflammatory bowel disease (IBD), we studied the influence of genetic and shared environmental risk factors in a twin cohort of IBD.

Material and methods: We analysed eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in faecal samples from twin pairs with Crohn's disease (n = 37) or ulcerative colitis (n = 21) and from external healthy controls (n = 44). Eosinophils stained with eosinophil peroxidase (EPO) were quantified in rectal biopsies. Ratios with 95% confidence intervals were calculated.

Results: Twins with Crohn' disease displayed higher levels of EDN (Ratio = 2.98, 1.65-5.37) and ECP (Ratio 1.83, 1.24-2.70) than their healthy siblings. Levels did not differ between healthy twin-siblings and external controls (EDN, Ratio = 1.52, 0.79-2.94 and ECP, Ratio = 0.93, 0.56-1.54). Higher levels of EDN (Ratio = 2.43, 1.13-5.24) and ECP (Ratio = 1.53, 0.92-2.53) were observed among twins with ulcerative colitis vs their healthy siblings. Levels did not differ between healthy twin-siblings and external controls (EDN, Ratio = 1.08, 0.51-2.25 and ECP, Ratio = 1.29, 0.74-2.26). Using intra-class correlation coefficient (ICC), we found no agreement in levels of EDN or ECP in discordant pairs, except for ECP in monozygotic Crohn's disease pairs (ICC = 0.63). In contrast, agreement was observed in monozygotic pairs concordant for Crohn's disease (EDN, ICC = 0.67 and ECP, ICC = 0.66). The number of eosinophils in rectum was increased in twins with ulcerative colitis vs their healthy sibling (Ratio = 2.22, 1.50-3.27).

Conclusions: Activation of eosinophils in IBD seems to be a consequence of inflammation rather than an effect of genetic and shared environmental risk factors alone.

Keywords: Inflammatory bowel disease; eosinophils; faecal markers; twins.

MeSH terms

  • Eosinophil Cationic Protein
  • Eosinophil Granule Proteins
  • Eosinophil-Derived Neurotoxin
  • Eosinophils*
  • Humans
  • Inflammatory Bowel Diseases* / genetics
  • Risk Factors

Substances

  • Eosinophil Granule Proteins
  • Eosinophil-Derived Neurotoxin
  • Eosinophil Cationic Protein