Correlation of Chimerism with Acute Graft-versus-Host Disease in Rats following Liver Transplantation

The accurate diagnosis of acute graft-versus-host disease following liver transplantation (LTx-aGVHD) has been hampered. Chimerism appears in the majority of recipients after LT and its significance in the diagnosis of LTx-aGVHD has not been clearly established. To demonstrate the significance of chimerism on the diagnosis of LTx-aGVHD, we compared the change of chimerism in syngeneic LT recipients, semiallogeneic LT recipients, and LTx-aGVHD induced recipients. Chimerism in PBMCs following sex-mismatched LT was identified by real-time PCR based on a rat Y-chromosome-specific primer. All recipients in semiallogeneic group grew in a normal pattern. However, when donor splenocytes were transferred simultaneously during LT, the morbidity of lethal aGVHD was 100%. The chimerism appeared slightly higher in the semiallogeneic group than in the syngeneic LT group, but the difference was not significant. However, when the recipients developed lethal aGVHD after LT, chimerism in the PBMCs increased progressively, and even at an early time, a significant increase in chimerism was observed. In conclusion, high level chimerism correlated well with LTx-aGVHD, and detection of chimerism soon after transplantation may be of value in the diagnosis of LTx-aGVHD prior to the onset of symptoms.

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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

Blood ◽

10.1182/blood.v122.21.4602.4602 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4602-4602

Author(s):

Aining Sun ◽

Chengsen Cai ◽

Guanghua Chen ◽

Jun Wang ◽

Wu Depei

Keyword(s):

Graft Versus Host Disease ◽

Poor Prognosis ◽

Plasma Concentrations ◽

Response To Therapy ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

The Difference ◽

High Level ◽

Acute Graft

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.

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