1 REG3α IS A BIOMARKER OF GRAFT VERSUS HOST DISEASE OF THE GASTROINTESTINAL TRACT
A.C. Harris, J.L. Ferrara, J.E. Levine, T. Braun, J. Crawford, J. Granger, M. Vander Lugt, C. Byersdorfer, J. Magenau, A. Gomez, S. Choi, C. Kitko, G. Yanik, E. Peres, A. Pawarode, S. Mineishi, P. Reddy, D.R. Couriel, S. Paczesny Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI; J. Hogan, S. Pitteri, H. Wang, A. Chin, Q. Zhang, S. Hanash Molecular Diagnostics Laboratory, Fred Hutchinson Cancer Research Center, Seattle, WA.
CURRENT CATEGORY: Gastroenterology/Clinical Nutrition
ABSTRACT BODY: There are no validated plasma biomarkers specific to graft versus host disease (GVHD) of the gastrointestinal (GI) tract. Previously we identified and validated elafin as a plasma biomarker for skin GVHD using an unbiased proteomics discovery approach (Science Transl Med, 2010). Using this same proteomics approach to analyze plasma pooled from ten patients with and without the disease, we identified 76 plasma proteins that were increased at least two fold in patients with acute GI GVHD. REG3α, a C-type lectin antimicrobial protein secreted by Paneth cells, emerged as the lead candidate from among proteins that were preferentially expressed in the GI tract and measurable by ELISA. We analyzed plasma levels of REG3α in a validation set of 570 BMT patients: 113 GI GVHD; 223 no GVHD; 52 non-GVHD (e.g. infectious) enteritis; and 182 skin only GVHD. Unrelated and HLA-mismatched donors were over-represented in the GVHD groups; groups were otherwise balanced for age, myeloablative conditioning and date of sample collection. REG3α levels were more than twice as high in the GI GVHD group compared to all others (mean SEM in ng/ml: 245±40, 64±8, 74±18, 112±22, respectively, p<0.004). REG3α could distinguish GVHD from other causes of enteritis with an area under the curve (AUC) of the receiver operating characteristic (ROC) curve of 0.75 (95%CI, 0.66-0.82). Importantly, high REG3α levels at onset of …