Background: REG3 alpha has been recently shown to be a highly accurate biomarker for graft-versus-host-disease (GvHD). Given the unmet need of such biomarkers in Crohn's disease (CD) and the similarities between CD and GvHD, we aimed at investigating the role of serum REG3 alpha as a diagnostic and prognostic biomarker in CD patients undergoing autologous hemopoetic stem cell transplantation (HSCT) in the multicenter Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) trial and to compare it to C-reactive protein (CRP). Methods: Stored serum samples from the ASTIC trial were analyzed using a commercially available human PAP1 ELISA-kit to measure REG3 alpha levels. CRP was available from prior analysis in the ASTIC trial. These levels were correlated with clinical and endoscopic disease activity as well as overall clinical and endoscopic outcome 1 year after autologous HSCT. Results: One hundred thirty two serum samples were available for analysis. The mean concentration of REG3 alpha was 101.8 ng/ml (95% CI 22.6-258.3). No significant elevation of REG3 alpha was found among patients with active disease compared to those in remission (106.3 vs. 91.4). Patients with moderate to severe endoscopic disease activity showed substantially, although not significantly elevated REG3 alpha levels compared to those in remission (95.4 vs. 52.4, p = 0.052). Baseline serum REG3 alpha levels of patients without clinical or endoscopic remission 1 year after HSCT were not elevated compared to those in remission (63.1 vs. 66.9, and 68.4 vs. 59.2, respectively). In contrast, CRP was significantly elevated in patients with active disease compared to patients in remission (14.1 vs. 6.0 mg/dI, p = 0.032). In addition, CRP was elevated, although not significantly, in patients with severe endoscopic disease compared to those in endoscopic remission (18.7 vs. 4.1, p = 0.062). Furthermore, baseline CRP was reduced in patients with clinical and endoscopic remission after HSCT compared to those without remission, although not significantly (8.8 vs. 21.4, n.s. and 8.1 vs. 12.4, n.s.). Conclusion: Given the divergent findings compared to GvHD, we conclude that serum REG3 alpha is not an accurate diagnostic and predictive biomarker in CD patients undergoing HSCT. In contrast, CRP is a valuable biomarker in order to differentiate active disease from remission. However, CRP does not seem to be of prognostic value for HSCT outcome. (C) 2015 S. Karger AG, Basel