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

• Published in: Clinical chemistry and laboratory medicine Vol. 54; no. 2; p. 249
• Main Authors: Pavlidis, Polychronis, Komorowski, Lars, Teegen, Bianca, Liaskos, Christos, Koutsoumpas, Andreas L, Smyk, Daniel S, Perricone, Carlo, Mytilinaiou, Maria G, Stocker, Winfried, Forbes, Alastair, Bogdanos, Dimitrios P
• Format: Journal Article
• Language: English
• Published: Germany 01-02-2016
• Subjects: Adult; Antibodies - blood; Autoantibodies - blood; Biomarkers - blood; Colitis, Ulcerative - blood; Colitis, Ulcerative - diagnosis; Crohn Disease - blood; Crohn Disease - diagnosis; Female; HEK293 Cells; Humans; Immunoglobulin A - blood; Immunoglobulin G - blood; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Middle Aged; Phenotype; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Saccharomyces cerevisiae - immunology
• ISSN: 1437-4331
• DOI: 10.1515/cclm-2015-0376

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.
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.
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.
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.