The major findings of the present study are that anti-GP2 antibodies are present in approximately 30% of patients with CD, and appear to identify cases with an earlier onset, ileocolonic location, and stricturing behaviour with perianal disease. Our findings support the notion that anti-GP2 antibodies are diagnostically and clinically-relevant markers of CD and can assist physicians in the management of patients with clinical suspicion of IBD. Not only anti-GP2 antibody testing by ELISA shows a remarkable positive correlation with PAB by IIF but also appears to allow better discrimination of low titre or borderline positive PAB by IIF and seems therefore more specific for CD than PAB testing. This supports the notion that anti-GP2 antibody detection can be a supplementary tool for the testing of CD-specific pancreatic antibodies complementing or even replacing the laborious IIF technique [2
Cohorts from clinical centres recruiting patients participating in the present study reported a ~30% anti-GP2 seropositivity in patients with CD [18
]. However, accurate estimation of the overall prevalence of anti-GP2 antibodies in patients with IBD could not be carried out up so far, as testing of serum samples was performed in different laboratories and at various time points [18
]. The systematic approach used in the present study, employing simultaneous testing of all coded samples in one laboratory and by the same immunodiagnostician (DRo), allowed for continuity of testing, thus permitting safer conclusions regarding the exact frequency of anti-GP2 antibodies in IBD. The approximately 30% anti-GP2 seropositivity rate may indeed be an underestimation of the real prevalence in newly diagnosed cases with CD, if antibodies are diminished over the course of the disease as an effect of the administration of biological agents and immunosuppressive treatment for CD [2
]. In fact, sharp decline of IgG anti-GP2 antibodies has been described in CD during a 12-month course with infliximab. Intriguingly, such conversion from seropositivity to seronegativity was not accompanied by simultaneous reduction of ASCA [19
An experienced group of Investigators from Belgium have tested 164 patients with CD for anti-GP2 antibodies, using the commercially-available assay which was used in the present study [21
]. Op De Beéck et al. reported a sensitivity of anti-GP2 antibodies in patients with CD of 21%. However, it is not clear at what time points these serum samples were tested for autoantibody reactivity [21
]. Also, the overall prevalence of PAB in the Belgian CD cohort was significantly lower than that of the present study (31% vs. 44%), and therefore a lower prevalence of anti-GP2 in the Belgian IBD population was not a surprising finding. The strikingly negative correlation between lower gastrointestinal tract localization of Crohn’s disease and presence of anti-GP2 was a characteristic feature of both studies. Finally, Op De Beéck et al. have failed to associate anti-GP2 seropositivity with other clinical correlates, when we have found that the presence of these antibodies is more prevalent in patients who present with CD at a younger age, in addition to those with stricturing disease behaviour. Immediate comparisons of the statistical values amongst the two studies cannot be made, as the Belgian study has been published in the form of a short Letter to the Editor with limited access to the wealth of the statistical analyses’ data [19
]. Even if there was a consensus amongst the two studies, it would be very premature to comment on the clinical significance of anti-GP2 antibodies in IBD, as the clinical relevance of these antibodies cannot be assessed based on two studies. Care must be exercised also, when extrapolating conclusions regarding the effect of biological agents in the behaviour of anti-GP2 antibodies as the Belgian investigators did not find a profound effect of infliximab and adalimumab in patients followed up for 6–44
Exchange of serum samples among researchers and large, multi-centre, prospective studies are needed to better delineate the diagnostic and clinical relevance of anti-GP2 pancreatic antibodies and their behaviour over the course of the disease in patients with inflammatory bowel diseases.
The development of a commercially-available ELISA based on recombinant human GP2 will allow for the accurate detection of GP2-specific pancreatic autoantibodies in routine laboratory practice and the initiation of longitudinal studies [18
]. It would be of interest to know whether such studies will provide independent verification of the thesis supported by the present data that combined anti-GP2 and ASCA testing performs better than relying on tests limited to ASCA alone.