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

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
• twins
• faecal markers

Acknowledgement

We thank Ingrid Stolt for skilful assistance in preparations of samples and assessment of eosinophil markers. We also thank Åke Öst for histological assessment.

Disclosure statement

JH has served as speaker and/or advisory board member for AbbVie, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, MEDA, Medivir, MSD, Novartis, Olink Proetomics, Pfizer, Prometheus Laboratories, Sandoz, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, and UCB. He also received grant support from Janssen, MSD and Takeda. IS has received lecture fees from Meda and Nutricia. MC has served as a speaker and/or advisory board member for Janssen, Pfizer, Takeda and Vifor Pharma. For the remaining authors none were declared.

Additional information

Funding

This work was supported by Medical Faculty, Uppsala University, Uppsala, Sweden.