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, REG3␣, by ELISA in samples from 1014 HCT patients from 3 transplantation centers. Plasma REG3␣ concentrations were 3-fold higher in patients at GI GVHD onset than in all other patients and correlated most closely with lower GI GVHD. REG3␣ 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 REG3␣ 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). REG3␣ is a plasma biomarker of GI GVHD that can be combined with clinical stage and histologic grade to improve risk stratification of patients. (Blood. 2011;118(25): 6702-6708)

The lower gastrointestinal tract (LGI) and liver are the GVHD target organs most associated with treatment failure and nonrelapse mortality. We recently identified regenerating islet-derived 3-␣ (REG3␣) as a plasma biomarker of LGI GVHD. We compared REG3␣ with 2 previously reported GI and liver GVHD diagnostic biomarkers, hepatocyte growth factor (HGF) and cytokeratin fragment 18, in 954 hematopoietic cell transplantation patients. All 3 biomarkers were significantly elevated in LGI GVHD compared with non-GVHD diarrhea; REG3␣ discerned LGI GVHD from non-GVHD diarrhea better than HGF and cytokeratin fragment 18. Although all 3 biomarkers predicted nonresponse to therapy at day 28 in LGI GVHD patients, only REG3␣ and HGF concentrations predicted 1-year nonrelapse mortality (P ‫؍‬ .01 and P ‫؍‬ .02, respectively). Liver GVHD without GI involvement at GVHD onset and non-GVHD liver complications were uncommon; all 3 biomarkers were elevated in liver GVHD, but did not distinguish GVHD from other causes of hyperbilirubinemia. (Blood. 2012;119(12): 2960-2963)

Admission resistin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Resistin may have potential for clinical use as a new and diagnostic serum marker.

Resistin, and to a lesser extent leptin, but not adiponectin levels are novel potential markers for extrapancreatic necrosis and severity of acute pancreatitis and should therefore be tested in larger cohorts of patients.

Induction of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation along the kynurenine pathway, acts as a potent immunoregulatory loop. To address its role in human allogeneic stem cell transplantation, we measured major tryptophan metabolites, such as quinolinic acid and kynurenine, in serial urine specimens from 51 patients by liquid chromatography-tandem mass spectrometry. Samples were collected between admission and day 90 after transplantation, and metabolite levels were correlated with early clinical events and outcome. In selected patients, IDO gene expression was assessed by quantitative RT-PCR in intestinal biopsies. Surviving patients had significantly lower metabolite levels on days 28, 42, and 90, respectively, compared with patients dying of GVHD and associated complications (n = 10). Kynurenine levels were directly correlated with severity and clinical course of GVHD: Mean urinary quinolinic acid levels were 4.5 ± 0.3 μmol/mmol creatinine in the absence of acute GVHD, 8.0 ± 1.1 μmol/mmol creatinine for GVHD grade 1 or 2, and 13.5 ± 2.7 μmol/mmol creatinine for GVHD grade 3 or 4 (P < .001), respectively. GVHD-dependent induction of IDO was further suggested by increased expression of IDO mRNA in intestinal biopsies from patients with severe GVHD. Our data indicate reactive release of kynurenines in GVHD-associated inflammation.