Abstract
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.
Acknowledgments:
We thank Dr. Eirini I. Rigopoulou for critical reading of the manuscript and helpful comments concerning the statistical analyses.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Guarantor of the article: Dimitrios P. Bogdanos, MD, PhD. DPB and LK planned and designed the study, and drafted the manuscript. PP analysed the data and drafted the manuscript. LK, BT, WS developed the assay, conducted testing, and contributed to data analysis. CL, MGM conducted testing. PP, ALK, and AF provided biological material and clinical information related to the clinical biomaterial. DSS and CP reviewed the manuscript and contributed considerably to its final drafting. All authors analysed the results and critically reviewed the manuscript.
Research funding: EUROIMMUN provided kits and reagents for the study free of charge.
Employment or leadership: LK, BT are employees of EUROIMMUN; WS is a shareholder of EUROIMMUN. Others: All other authors had no disclosures relevant to this manuscript.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Article note:
Part of this work was presented as a poster presentation in DDW 2013 (abstract: Pavlidis et al. ‘Su1201 diagnostic and clinical significance of the pancreatic autoantibodies anti-GP2 and anti-CUZD1 in inflammatory bowel diseases’. Gastroenterology 2013;144:S425–6).
Supplemental Material:
The online version of this article (DOI: 10.1515/cclm-2015-0376) offers supplementary material, available to authorised users.
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