Human glycoprotein-2 expressed in Brunner glands-A putative autoimmune target and link between Crohn's and coeliac disease

Glycoprotein 2 (GP2) is an autoantigen in Crohn's (CD) and coeliac disease (CeD). We assessed GP2-isoform (GP21-4)-expression in intestinal biopsies of paediatric patients with CD, CeD, ulcerative colitis (UC), and healthy children (HC). Transcription of GP21-4 was elevated in proximal small intestine in CeD and CD patients (only GP22/4) compared to jejunum (CeD/CD) and large bowel (CD). CeD patients demonstrated higher duodenal GP22/4-mRNA levels compared to HC/UC patients whereas CD patients showed higher GP24-mRNA levels compared to UC patients. Duodenal synthesis of only small GP2 isoforms (GP23/4) was demonstrated in epithelial cells in patients/HC and in Brunner glands (also large isoforms) with a more frequent apical location in CD/CeD patients. All four GP2 isoforms interacted with gliadin and phosphopeptidomannan. Gliadin digestion improved binding to GP2 isoforms. GP21-4 binding to CeD/CD-related antigens, elevated duodenal GP21-4-mRNA transcription, and GP2-protein secretion in Brunner glands of CeD/CD patients suggest an autoimmune CeD/CD link.

Automated summary

This study examined the expression of GP2-isoform (GP21-4) in intestinal biopsies of pediatric patients with Crohn's disease (CD), coeliac disease (CeD), ulcerative colitis (UC), and healthy children (HC). The results showed that transcription of GP21-4 was elevated in the proximal small intestine in CeD and CD patients, and CeD patients had higher levels of duodenal GP22/4-mRNA compared to HC/UC patients. Duodenal synthesis of small GP2 isoforms was demonstrated in epithelial cells and Brunner glands, with a more frequent apical location in CD/CeD patients. All four GP2 isoforms interacted with gliadin and phosphopeptidomannan. Gliadin digestion improved binding to GP2 isoforms. The findings suggest an autoimmune link between CeD/CD and GP2.