Diagnostic and clinical significance of Crohn's disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies

Polychronis Pavlidis, Lars Komorowski, Bianca Teegen, Christos Liaskos, Andreas L Koutsoumpas, Daniel S Smyk, Carlo Perricone, Maria G Mytilinaiou, Winfried Stocker, Alastair Forbes, Dimitrios P Bogdanos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


BACKGROUND: Pancreatic autoantibodies (PAB) targeting GP2 and CUZD1 are Crohn's disease (CrD)-markers. The clinical significance of anti-GP2 antibodies has been assessed, but that of anti-CUZD1 remains elusive. The aim of the study was to assess the clinical utility of anti-CUZD1/anti-GP2 by novel cell-based indirect immunofluorescence (IIF) assays in CrD.

METHODS: A total of 212 CrD and 249 UC patients followed up at a London IBD centre were investigated to simultaneously detect PABs, anti-GP2 and anti-CUZD1 by IIF using primate pancreatic tissue, and HEK293 over-expressing CUZD1 or GP2.

RESULTS: Overall, 88 (41.5%) CrDs compared to 26 (10.4%) UCs (p<0.001) tested positive for IgA and/or IgG anti-GP2 and/or anti-CUZD1 antibodies, while ASCA were found in 67.5% CrDs versus 19.2% UCs (p<0.0001); ASCA and/or PAB (anti-GP2 or anti-CUZD1) were detected in 76% CrD versus 34% UC patients. IgG anti-GP2 antibodies were less prevalent in L2 phenotype (p=0.002) and more prevalent in patients with stricturing disease (p=0.0418), even when a higher cut-off (≥1000 RU) was used (p=0.0396). Also, anti-GP2 IgG positive CrD patients had younger age of disease onset. IgA and/or IgG ASCA and anti-GP2 IgG antibody positive CrDs had younger onset of disease (p<0.0001), were more likely to have both ileal and colonic disease (p<0.0001) and had more stricturing (p<0.0001) than seronegative patients. Clinical correlates were not found for anti-CUZD1 positivity.

CONCLUSIONS: PAB testing increases ASCA's serological sensitivity for CrD. Anti-GP2 detection, in isolation or in combination with ASCA, stratify CrD patients who phenotypically are characterised by a much younger onset of disease, extensive and stricturing behaviour.

Original languageEnglish
Pages (from-to)249-56
Number of pages8
Issue number2
Early online date18 Jul 2015
Publication statusPublished - Feb 2016


  • Adult
  • Antibodies
  • Autoantibodies
  • Biomarkers
  • Colitis, Ulcerative
  • Crohn Disease
  • Female
  • HEK293 Cells
  • Humans
  • Immunoglobulin A
  • Immunoglobulin G
  • Male
  • Membrane Glycoproteins
  • Membrane Proteins
  • Middle Aged
  • Phenotype
  • Recombinant Proteins
  • Saccharomyces cerevisiae


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