High Plasma Level Of Regenerating Islet-Derived 3-Alpha (Reg3a) Protein Predicts Grade 3-4 Lower Gastrointestinal Acute Graft-Versus-Host Disease and Poor Prognosis

Objective To explore the feasibility of applying plasma Reg3α protein level for the diagnosis and prognosis of the lower gastrointestinal acute graft-versus-host disease(LGI-aGVHD). Method One hundred and three patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital from December 2011 to December 2012 were included in this prospective study. Peripheral blood samples were collected from allo-HSCT recipients at -9d, 0d, +14d, +28d, at the time when they developed aGVHD, and at the one and four weeks after aGVHD therapy. The plasma concentrations of Reg3α protein were measured by ELISA assay. Results Of the 103 patients, 17 subjects never developed aGVHD symptoms (no-aGVHD), 27 subjects presented with non-aGVHD associated diarrhea, 10 subjects presented with isolated skin aGVHD, 17 subjects developed grades ±-II LGI-aGVHD, 32 subjects developed grades III-‡W LGI-aGVHD. The plasma concentrations of Reg3α in patients with LGI-aGVHD vs non-aGVHD diarrhea were 111.5(54.7-180.2) vs 23.9 (14.5-89.5) ng/ml respectively, with the difference being statistically significant ( P <0.001). The plasma concentrations of Reg3α in 17 patients who had no response to therapy at 4 weeks for grades III-‡W LGI-aGVHD and 7 patients who experienced a complete or partial response were 137.2(51.7-205.4) and 679.4(122.3-896.8) ng/ml respectively, with the difference being statistically significant ( P =0.028). All of the patients who had no response to therapy died of aGVHD-associated multiple organ failure. The area under the ROC curve was 0.902 when plasma concentration of Reg3α was set at 87.73 ng/ml. The sensitivity was 81.48% and the specificity was 82.86% when the critical value was used in diagnosis of grades III-‡W LGI-aGVHD. The probability of grades III-‡W LGI-aGVHD had statistical difference above and below 87.73 ng/ml after allo-HSCT( P <0.001). Conclusion The high level of plasma Reg3α protein after transplantation predicts grades III-‡W LGI-aGVHD. In grades III-‡W LGI-aGVHD patients receivingimmunosuppressive treatment at four weeks, the high level of plasma Reg3α protein correlates withs a poor prognosis. The plasma concentrations of Reg3α can be used as a specific biomarker of LGI-aGVHD. Disclosures: No relevant conflicts of interest to declare.