| Backgroud: Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is an effective therapy for patients with hematological malignancies, aplastic anemia, autoimmune diseases and some solid tumors. Although in the past decades many advances and improvements have been achieved, graft-versus host disease (GVHD) remains a major complication and the main death cause. The incidence of GVHD, thought to be mediated by donor T cells, lies in three main processes: (1) Transplant preparative conditioning regimen and infection initiate a cascade of pro-inflammatory cytokine release, which up-regulate the expression of HLA in target tissues. (2) Donor T cells recognize major histocompatibility antigens on recipient target cells, this make donor T cells activate and expanse, then IL-2R(CD25) rapidly express and lead to the secretion of pro-inflammatory cytokine such as IL-2. (3) IL-2 activates donor T cells engrafted in recipient, T cells promote "cytokine storm" leading to the massively secretion of inflammatory cytokines and develop GVHD. The NF -κB family has emerged as a key transducer of inflammatory signals involved in dendritic cell (DC) maturation and T lymphocyte activation. The transcription factor NF-κB has been demonstrated to play a pivotal role in cytokine signaling and the generation of cell-mediated immune responses in many exvivo models. The proteasome inhibitor bortezomib(Velcade) has been demonstrated to exert numerous biological effects that include blocking the activation of NF-κB. In Blanco's study, bortezomib induces selective apoptosis and decrease of Th1 responses among alloreactive T lymphocytes. Sun's study found that lethal GVHD could be prevented by the administration of bortezomib.These results confirm critical role for NF-κB in the pathophysiology of GVHD and indicate that specific inhibition of NF-κB may constitute a viable therapeutic approach to reduce GVHD severity. Yet the research on the correlation between the NF-κB and the GVHD of transplanted patients has been mostly limited.Objective: To investigate the correlation among the expression of the NF-κB in the peripheral blood mononuclear cell (PBMC), GVHD, bilirubin and infection, for the patients after Allo-HSCT.Method: A total of sixteen patients having Allo-HSCT done in West China Hospital of Sichuan University from September 2006 to April 2007 were studied, and twenty-two healthy volunteers are used as normal control group. There are two cases having acute myeloid leukemia, two cases having acute lymphoblastic leukemia, twelve cases having chronic myeloid leukemia. The average age of these patients is 36.8, and thirteen of them are male while three of them are female. Peripheral intravenous blood(3-5ml) was collectted from the patients with white blood cells (WBC) exceeding 1×109/L in two to three weeks post transplant. After mononuclearcells was isolated with human lymphocyte separating medium, the total RNA of PBMCs was extracted by Trizol and transcribed into cDNA. The expression of the NF-κB was tested by Reverse transcription PCR. Furthermore, symptoms associated with GVHD in the patients, nursing record and examination findings such as Routine blood tests, biochemistry and so on, are recorded. The data were analyzed by SPSS13.0 statistical soft-ware, a equals 0.05 were considered significant test level.Results:(1) The average expression of the NF-κB in the PBMC from the patients after Allo-HSCT and that from the normal control group as reference are 0.3869 and 0.1627, respectively, which shows that there is significant difference between them (p＜0.01).(2) The average expression of NF-κB of the patients with aGVHD is higher than that of the patients without aGVHD (p＜0.025). The average expression of the NF-κB of the patients without GVHD is at the same level of that of the normal control group(p＞0.05).(3) The linear correlation coefficient between the expression of NF-κB and the bilirubin is +0.4927 (p＜0.05), which shows positive linear correlativity between them in some acceptable degree.(4) The Spearman rank correlation coefficient between the expression of NF-κB and the degree of aGVHD is+0.46 (p＜0.05), which shows positive rank correlativity between them.(5) The infection contributes to the expression of NF-κB: The average expressive intensity of the NF-κB of the patients with GVHD is remarkably higher than that of the normal control group. However, all these sixteen patients have infection in some high or low degree, and those with GVHD have comparatively worse infection than those without GVHD. Therefore, the infection might be one of the reasons for the increase of the expression of NF-κB of the patients with GVHD.Conclusion: The average expressive level of the NF-κB in the PBMC from the patients after Allo-HSCT is significantly higher than that from the healthy people, which shows difference in the statistical point of view (p＜0.05). The average expressive level of the NF-κB of the patients with aGVHD is higher that that of the patients without aGVHD(p＜0.025); There is positive rank correlativity between the expressive level of NF-κB and the degree of aGVHD, with the rank correlation coefficient be +0.46(p＜0.05). There is positive linear correlativity in some acceptable degree between the expressive level of the NF-κB and the value of bilirubin, with the correlation coefficient be +0.4927(p＜0.05). Serious infection might be one of the reasons for the increase of the expressive level of the NF-κB.
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