ABSTRACT
Objective To analyze the predictive value of serum interleukin-27 (IL-27) for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated donors. Methods Serum samples were collected from 72 patients after receiving allo-HSCT from unrelated donors during January to December 2012. Serum samples collected from 70 patients received allo-HSCT in 2013 were used for confirmation. All patients received myeloablative conditioning regimen prior to allo-HSCT. Cyclosporin A (CsA)+mycophenolate mofetil (MMF)+short-term methotrexate (MTX) were used for GVHD prophylaxis. Serum IL-27 levels in patients with aGVHD were measured by ELISA. The pre-dictive value of IL-27 index,defined as the ratio of serum IL-27 level at neutrophil engraftment to that before pre-conditioning regimen, for allogeneic HSCT was retrospectively analyzed. Results Serum IL-27 index was significantly decreased in patients with gradeⅡ-ⅣaGVHD(grade 0-Ⅰ : 1.89±0.68 vs gradeⅡ-Ⅳ :1.26±0.49;P<0.000 1). IL-27 index had good value for grade Ⅱ-Ⅳ aGVHD (AUC=0.782,95% CI:0.675-0.889,P<0.001). Patients with a lower serum IL-27 index (<1.33) were more likely to have a higher cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with a higher serum IL-27 index (P<0.001). Multivariate analysis confirmed that low IL-27 index was the most significant risk factor for gradeⅡ-Ⅳ aGVHD (HR=4.50,95% CI:2.1-9.8,P<0.01). These findings were consistent with the results found in the serum samples collected in 2013. Conclusion Low IL-27 index could be used to predict the incidence of grade Ⅱ-Ⅳ acute GVHD after allo-HSCT from unrelated donors.
ABSTRACT
Allogeneic hematopoietic stem cell transplantation ( allo-HSCT) is an effective therapy for the treatment of various malignant and non-malignant hematological diseases. Acute graft-verse-host-dis-ease ( aGVHD) , a major complication following allo-HSCT, is one of the predominant causes of GVHD-re-lated mortality. The development of aGVHD is a typical pathologic process with the release of inflammatory cytokines in great quantities, resulting in the occurrence ofcytokine storm and causing specific pathologi-cal damages by attacking the recipient organ. Therefore, identification of biomarkers specific for aGVHD of-fers promise to the treatment of aGVHD. In this review, we summarizes the functions of several typical in-flammatory cytokines, including IL-1β, IL-6, IL-17A and IL-10, and their mechanisms in the development of aGVHD in order to provide references for the prevention and treatment of aGVHD.
ABSTRACT
Objective To investigate the role of FTY720, an agonist of the sphingosine 1-phos-phate (S1P) receptor, in acute graft-versus-host disease (aGVHD) caused by allogeneic hematopoietic stem cell transplantation and to further elucidate its possible mechanism .Methods BALB/c ( H2 d ) recipient mice were given whole body lethal irradiation (750 cGy) for 4 hours.A mouse model of aGVHD was estab-lished by intravenously injecting recipient mice with 1×107 C57BL/6 (H2b) mice derived bone marrow cells (BMCs) and 5×106 whole splenic cells.FTY720 (3 mg/kg) was intraperitoneally injected into recipient mice from the day before allogeneic bone marrow transplantation ( allo-BMT) to day 4 thereafter to monitor the survival rate .The mice in control group were perfused with equal volume of control reagent .Fluores-cence-activated cell sorting ( FACS) was used to analyze the phenotypes of immune cells in spleen , liver, lung as well as intestines of mice on the fourth day of allo-BMT with or without FTY720 treatment. Results FTY720 significantly prolonged overall survival in mice with allo-BMT induced aGVHD .FACS analysis showed that FTY720 significantly inhibited the distribution of matured dendritic cells ( DCs) in lung and small intestines .Conclusion FTY720 could significantly alleviate the symptom of aGVHD in mice re-ceived allogeneic hematopoietic stem cell transplantation .The possible mechanism might be associated with the inhibited distribution of matured DCs in lung and intestines .