Background & Aims: In most cases celiac disease (CD) is successfully treated with a gluten-free diet (GFD). However, some patients become refractory to the GFD. Refractory CD (RCD) patients have an increased risk for developing enteropathy associated T-cell lymphoma and early diagnosis is therefore of importance. Currently, RCD diagnosis relies on endoscopy and adequate serological markers are lacking. Antibodies against glycoprotein-2 (GP2A) were described in Crohn's disease (CrD) and active CD but not in ulcerative colitis (UC), suggesting this is a specific marker for small intestinal lesions.

 Sera obtained from patients visiting our outpatient clinic for routine serological tests for diagnosis and/or follow-up of inflammatory bowel disease (n=78), active CD (n=45), GFD (n=34) and RCD (n=15) were analysed for GP2A titres.

Results: Increased GP2A-IgA levels in CrD and active CD as compared to controls (p<0.001) and lack thereof in UC was confirmed. However, we could not confirm the association with small bowel localization within the CrD patient group. Within CD patients, we demonstrated a significant decrease of GP2A-IgA titres upon a GFD and increased levels in RCD patients as compared to patients on a GFD. Although GP2A-IgA was not associated with the degree of villous atrophy, GP2A-IgA levels were able to distinguish RCD patients from GFD patients (ROC AUC=0.79, p=0.002).

Conclusion: Follow-up of GP2A-IgA titres in CD patients on a GFD may help to identify patients at risk for developing RCD.

Abbreviations: ABSA: anti-bovine serum albumine; ASCA: anti- Saccharomyces cerevisiae antigen; AU:
artificial units; AUC: area under the curve; CD: celiac disease; CrD: Crohn's disease; EATL: enteropathy
associated T-cell lymphoma; EmA: anti-endomysium antibodies; GFD: gluten free diet; GP2A: glycoprotein 2 antibodies; IEL: intraepithelial lymphocytes; RCD: refractory celiac disease; ROC: receiver operator curve; TG2A: transglutaminase-2 antibodies; UC: ulcerative colitis.


Celiac disease, Crohn's disease, ulcerative colitis, refractory celiac disease, glycoprotein-2 antibodies