Glycoprotein 2 (GP2) is an autoantigen in Crohn's (CD) and coeliac disease (CeD). We assessed GP2-isoform (GP2_1–4)-expression in intestinal biopsies of paediatric patients with CD, CeD, ulcerative colitis (UC), and healthy children (HC). Transcription of GP2_1–4 was elevated in proximal small intestine in CeD and CD patients (only GP2_2/4) compared to jejunum (CeD/CD) and large bowel (CD). CeD patients demonstrated higher duodenal GP2_2/4-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 (GP2_3/4) 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. GP2_1–4 binding to CeD/CD-related antigens, elevated duodenal GP2_1–4-mRNA transcription, and GP2-protein secretion in Brunner glands of CeD/CD patients suggest an autoimmune CeD/CD link.