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The Authors' reply We would like to thank Op De Beéck et al1 for their interest in the evaluation of antibodies to the zymogen granule membrane glycoprotein 2 (GP2) in patients with inflammatory bowel disease (IBD). Their meticulous investigation of a large, well-characterised cohort of patients and controls revealed good reproducibility, linearity and robustness of the anti-GP2 assays, confirming the assay performance reported in a recent study by our group.2 Both studies found a comparable, high specificity of anti-GP2 for Crohn's disease (CD). On testing 100 patients with ulcerative colitis (UC) and 162 blood donors (BDs) as controls in our study, the specificity reached a value of 94.3% (95% CI 90.7% to 96.8%). This value is similar to the specificity of 93.9% reported by Op De Beéck et al, including 118 UC patients, 75 gastrointestinal controls and 100 BDs. However, UC patients do not seem to be an optimal disease control group regarding diagnostic specificity for CD. Clinical and histological findings do not allow differentiation between CD and UC in all cases. Therefore, patients with other intestinal diseases caused by infections, drugs and nutritional factors mimicking IBD should also be tested in further studies.
At variance with our study, Op De Beéck et al reported a lower sensitivity of anti-GP2 antibodies in CD of just 20.7% (34/164) compared with 30.1% (55/176) in our study (95% CI 24.2% to 38.2%). As both studies used an identical methodological approach and ELISA, technical reasons are unlikely to explain the difference, so the cause for the discrepancy may be related to different inclusion criteria of the patient cohorts.
In our study, IgG class anti-GP2 antibodies are closely associated with the occurrence of IgG antibodies to mannan of Saccharomyces cerevisiae (anti-Saccharomyces cerevisiae antibodies, ASCA) but anti-GP2 can also be present in ASCA seronegative cases (31/175), supporting the notion shared by Op De Beéck et al that anti-GP2 could be an interesting marker for antibody profiling in IBD.
Interestingly, apart from its main synthesis in pancreatic acinar cells, GP2 has been shown to be overexpressed at the site of inflammation in CD, but not UC patients, strongly supporting its possible pathophysiological role in IBD.3 Furthermore, GP2 synthesis has been reportedly demonstrated in intestinal M cells of intestinal Peyer's patches as a specific receptor targeting FimH positive bacteria for transcytosis. Recently, interaction of GP2 with scavenger receptors on endothelial cells has been shown and its uptake might have profound effects in antigen clearance and mediation of the immune response.4 5
Of clinical relevance, Op De Beéck et al found that all CD patients positive for anti-GP2 before treatment with infliximab remained positive with no major change in antibody concentration. Our experience includes a 44-year, Caucasian CD case with disease parameters characterised by colonic location (L2), onset of disease at 17 years (A2) and stricturing behaviour (B2) leading to ileocaecal resection 16 years ago. Due to persistent disease, infliximab was administered (300 mg every 7 weeks over a period of 12 months). This particular CD patient demonstrated a significant decrease of anti-GP2 IgG 12 months after starting the treatment with anti-TNFα, whereas there was no change in ASCA levels (figure 1). Therefore, in addition to clinical studies with large patient cohorts, prospective studies to investigate the clinical association of anti-GP2 levels with different clinical characteristics of CD patients and treatment response are warranted.
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Competing interests Dirk Roggenbuck is a shareholder of GA Generic Assays GmbH and Medipan GmbH. The remaining authors declare that they have no competing financial interests.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Medical Faculty, University of Dresden.
Provenance and peer review Not commissioned; not externally peer reviewed.
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