title: Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease.
abstract: There are no plasma biomarkers specific for GVHD of the gastrointestinal (GI) tract, the GVHD target organ most associated with nonrelapse mortality (NRM) following hematopoietic cell transplantation (HCT). Using an unbiased, large-scale, quantitative proteomic discovery approach to identify candidate biomarkers that were increased in plasma from HCT patients with GI GVHD, 74 proteins were increased at least 2-fold; 5 were of GI origin. We validated the lead candidate, REG3α, by ELISA in samples from 1014 HCT patients from 3 transplantation centers. Plasma REG3α concentrations were 3-fold higher in patients at GI GVHD onset than in all other patients and correlated most closely with lower GI GVHD. REG3α concentrations at GVHD onset predicted response to therapy at 4 weeks, 1-year NRM, and 1-year survival (P ≤ .001). In a multivariate analysis, advanced clinical stage, severe histologic damage, and high REG3α concentrations at GVHD diagnosis independently predicted 1-year NRM, which progressively increased with higher numbers of onset risk factors present: 25% for patients with 0 risk factors to 86% with 3 risk factors present (P < .001). REG3α is a plasma biomarker of GI GVHD that can be combined with clinical stage and histologic grade to improve risk stratification of patients.
authors: Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
authors: James L M
authors: JL
authors: Ferrara
authors: Andrew C
authors: AC
authors: Harris
authors: Joel K
authors: JK
authors: Greenson
authors: Thomas M
authors: TM
authors: Braun
authors: Ernst
authors: E
authors: Holler
authors: Takanori
authors: T
authors: Teshima
authors: John E
authors: JE
authors: Levine
authors: Sung W J
authors: SW
authors: Choi
authors: Elisabeth
authors: E
authors: Huber
authors: Karin
authors: K
authors: Landfried
authors: Koichi
authors: K
authors: Akashi
authors: Mark
authors: M
authors: Vander Lugt
authors: Pavan
authors: P
authors: Reddy
authors: Alice
authors: A
authors: Chin
authors: Qing
authors: Q
authors: Zhang
authors: Samir
authors: S
authors: Hanash
authors: Sophie
authors: S
authors: Paczesny
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D041981:Gastrointestinal Tract / Q000473:pathology; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D037181:Lectins, C-Type / Q000097:blood*; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D000073718:Pancreatitis-Associated Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human