Serum REG3alpha and C-Reactive Protein Levels in Crohn's Disease Patients Undergoing Immunoablation and Autologous Hemopoetic Stem Cell Transplantation in the ASTIC Trial.
BACKGROUND
REG3α 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 REG3α 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 REG3α 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 REG3α was 101.8 ng/ml (95% CI 22.6-258.3). No significant elevation of REG3α 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 REG3α levels compared to those in remission (95.4 vs. 52.4, p = 0.052). Baseline serum REG3α 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/dl, 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.).


CONCLUSIONS
Given the divergent findings compared to GvHD, we conclude that serum REG3α 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.
Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
Thomas
T
Greuter
Silvia
S
Lang
Ernst
E
Holler
Christopher J
CJ
Hawkey
Gerhard
G
Rogler
Luc
L
Biedermann
D000328:Adult; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D003113:Colonoscopy; D003424:Crohn Disease / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000069585:Filgrastim / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D037181:Lectins, C-Type / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D014182:Transplantation, Autologous; D055815:Young Adult
D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D003520:Cyclophosphamide; D002097:C-Reactive Protein; D000069585:Filgrastim