KIR配體—配體模式對無關(guān)供者造血干細胞移植預后評估的meta分析
發(fā)布時間：2019-05-16 12:54
【摘要】：背景：殺傷細胞免疫球蛋白樣受體(Killer cell immunoglobulin-like receptors,KIR)表達在NK細胞(Natural killer cell)表面并與人類白細胞抗原(Human leukocyte antigen, HLA) Ⅰ類分子相互作用傳遞抑制或者活化信號,從而影響NK細胞的功能。目前認為,當細胞表面不表達或者低表達(譬如感染或腫瘤)與KIR相應的HLA-I類分子時,NK細胞被激活,攻擊并溶解受到感染的細胞或瘤細胞。而供受者之間KIR與其配體的匹配模式以及匹配程度與造血干細胞移植主要并發(fā)癥及預后相關(guān),其中配體-配體模式被定義為供者包含的KIR配體中有患者所缺失的KIR配體存在。相關(guān)文獻顯示,KIR配體-配體模式與無關(guān)供者造血干細胞移植(Hematopoietic stem cell transplantation, HSCT)的預后密切相關(guān)。本文通過檢索1994-2012年期間的相關(guān)文獻進行meta分析為無關(guān)供者的選擇及HSCT風險預判提供參考。方法：檢索pub med、medline、Embase以及The Cochrane Library幾個數(shù)據(jù)庫中1994-2012年在線的相關(guān)文獻,以"Killer cell immunoglobulin-like receptors/KIR" "HSCT/hematopoietic stem cell transplantation"為關(guān)鍵字進行檢索。將檢索到的文獻根據(jù)納入標準逐一進行排除后獲得納入文獻。對納入文獻進行數(shù)據(jù)提取,需要提取的數(shù)據(jù)包括：病例數(shù)、患者平均年齡、HLA相合程度、干細胞來源、病種、疾病分期以及是否使用體外去除T細胞(T cell depleted,TCD)或抗胸腺細胞球蛋白(Anti-thymocyte globulin,ATG)等；觀察的效應指標：5年總生存率(Overall survival,OS),Ⅱ-Ⅳ級急性移植物抗宿主病(Acute graft-versus-host disease,acute GVHD)發(fā)生率,復發(fā)率(Relapse),移植相關(guān)死亡率(Transplant-related mortality,TRM)。提取數(shù)據(jù)后應用Revman 5.0對所獲得的數(shù)據(jù)進行分析。結(jié)果：通過關(guān)鍵詞"KIR/killer immunoglobulin like receptor"和"HSCT/hematopoieticstem cell transplantation"共檢索到197篇文獻,經(jīng)過篩選后納入7篇文獻,包括3845例患者。我們meta分析的結(jié)果顯示：供受者KIR配體匹配組較錯配組在OS上更具優(yōu)勢(OR：odds ratio=1.93,95% CI:95% confidence interval=1.03-3.61,P=0.04);然而,兩組在2-4度GVHD發(fā)生率(OR=0.94,CI=0.71-1.24,P=0.64),5年復發(fā)率(OR=1.05,CI= 0.75-1.47,P=0.77)以及TRM上并沒有顯著的差異(OR=0.61,CI=0.15-2.51,P=0.50)。結(jié)論：通過對KIR的配體-配體模式在無關(guān)供者HSCT的OS、Ⅱ-Ⅳ級GVHD、TRM以及復發(fā)率進行meta分析,我們發(fā)現(xiàn)無關(guān)供者造血干細胞移植供受者KIR配體匹配對患者的總生存更加有利,而在2-4度急性GVHD、復發(fā)及移植相關(guān)死亡率等方面則沒有顯著的差異,但是這種結(jié)果可能會受到HLA相合程度,T細胞去除以及疾病本身特性的影響。
[Abstract]:Background: killer cell immunoglobulin-like receptor (Killer cell immunoglobulin-like receptors,KIR is expressed on the surface of NK cell (Natural killer cell) and interacts with human leukocyte antigen (Human leukocyte antigen, HLA) class I molecules to transmit inhibitory or activation signals. Thus affecting the function of NK cells. At present, it is believed that when HLA-I molecules corresponding to KIR are not expressed or underexpressed on the surface of cells (such as infection or tumor), NK cells are activated, attacked and dissolved into infected cells or tumor cells. The matching pattern and degree of matching between donors and recipients of KIR and its ligands are related to the main complications and prognosis of hematopoietic stem cell transplantation, in which ligand-ligand pattern is defined as the presence of missing KIR ligands in KIR ligands contained in donors. The related literature shows that the KIR ligand-ligand model is closely related to the prognosis of unrelated donor hematopoietic stem cell transplantation (Hematopoietic stem cell transplantation, HSCT). In this paper, meta analysis is carried out by searching the relevant literature from 1994 to 2012 to provide a reference for the selection of unrelated donors and the prediction of HSCT risk. Methods: the relevant literatures of pub med,medline,Embase and The Cochrane Library from 1994 to 2012 were searched and searched with the keyword "Killer cell immunoglobulin-like receptors/KIR" and "HSCT/hematopoietic stem cell transplantation". The searched literature is excluded one by one according to the inclusion criteria and then included in the literature. The data to be extracted from the included literature include the number of cases, the average age of the patient, the degree of HLA coincidence, the origin of stem cells, the disease type, the stage of the disease, and whether to remove T cell (T cell depleted, in vitro. TCD) or antithymoglobulin (Anti-thymocyte globulin,ATG), etc. The 5-year overall survival rate (Overall survival,OS), the incidence of grade II-IV acute graft-versus-host disease (Acute graft-versus-host disease,acute GVHD) and the recurrence rate of (Relapse), transplantation-related mortality (Transplant-related mortality,TRM) were observed. After extracting the data, Revman 5.0 was used to analyze the obtained data. Results: a total of 197 articles were searched by the keywords "KIR/killer immunoglobulin like receptor" and "HSCT/hematopoieticstem cell transplantation". After screening, 7 articles, including 3845 patients, were included. The results of our meta analysis showed that the donor and recipient KIR ligand matching group had more advantages on OS than the mismatched group (OR:odds ratio=1.93,95% CI:95% confidence interval=1.03-3.61,P=0.04). However, there was no significant difference in the incidence of 2: 4 degree GVHD (OR=0.94,CI=0.71-1.24,P=0.64), 5-year recurrence rate (OR=1.05,CI= 0.75 鹵1.47, P = 0.77) and TRM between the two groups (OR=0.61,). CI=0.15-2.51,P=0.50) Conclusion: by meta analysis of OS, grade II-IV GVHD,TRM and recurrence rate of KIR ligand-ligand pattern in unrelated donor HSCT, we found that donor and recipient KIR ligand matching of unrelated donor hematopoietic stem cell transplantation was more beneficial to the total survival of patients. However, there was no significant difference in the recurrence of acute GVHD, and the mortality associated with transplantation, but this result may be affected by the degree of HLA coincidence, T cell removal and the characteristics of the disease itself.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R457.7
本文編號：2478293
[Abstract]:Background: killer cell immunoglobulin-like receptor (Killer cell immunoglobulin-like receptors,KIR is expressed on the surface of NK cell (Natural killer cell) and interacts with human leukocyte antigen (Human leukocyte antigen, HLA) class I molecules to transmit inhibitory or activation signals. Thus affecting the function of NK cells. At present, it is believed that when HLA-I molecules corresponding to KIR are not expressed or underexpressed on the surface of cells (such as infection or tumor), NK cells are activated, attacked and dissolved into infected cells or tumor cells. The matching pattern and degree of matching between donors and recipients of KIR and its ligands are related to the main complications and prognosis of hematopoietic stem cell transplantation, in which ligand-ligand pattern is defined as the presence of missing KIR ligands in KIR ligands contained in donors. The related literature shows that the KIR ligand-ligand model is closely related to the prognosis of unrelated donor hematopoietic stem cell transplantation (Hematopoietic stem cell transplantation, HSCT). In this paper, meta analysis is carried out by searching the relevant literature from 1994 to 2012 to provide a reference for the selection of unrelated donors and the prediction of HSCT risk. Methods: the relevant literatures of pub med,medline,Embase and The Cochrane Library from 1994 to 2012 were searched and searched with the keyword "Killer cell immunoglobulin-like receptors/KIR" and "HSCT/hematopoietic stem cell transplantation". The searched literature is excluded one by one according to the inclusion criteria and then included in the literature. The data to be extracted from the included literature include the number of cases, the average age of the patient, the degree of HLA coincidence, the origin of stem cells, the disease type, the stage of the disease, and whether to remove T cell (T cell depleted, in vitro. TCD) or antithymoglobulin (Anti-thymocyte globulin,ATG), etc. The 5-year overall survival rate (Overall survival,OS), the incidence of grade II-IV acute graft-versus-host disease (Acute graft-versus-host disease,acute GVHD) and the recurrence rate of (Relapse), transplantation-related mortality (Transplant-related mortality,TRM) were observed. After extracting the data, Revman 5.0 was used to analyze the obtained data. Results: a total of 197 articles were searched by the keywords "KIR/killer immunoglobulin like receptor" and "HSCT/hematopoieticstem cell transplantation". After screening, 7 articles, including 3845 patients, were included. The results of our meta analysis showed that the donor and recipient KIR ligand matching group had more advantages on OS than the mismatched group (OR:odds ratio=1.93,95% CI:95% confidence interval=1.03-3.61,P=0.04). However, there was no significant difference in the incidence of 2: 4 degree GVHD (OR=0.94,CI=0.71-1.24,P=0.64), 5-year recurrence rate (OR=1.05,CI= 0.75 鹵1.47, P = 0.77) and TRM between the two groups (OR=0.61,). CI=0.15-2.51,P=0.50) Conclusion: by meta analysis of OS, grade II-IV GVHD,TRM and recurrence rate of KIR ligand-ligand pattern in unrelated donor HSCT, we found that donor and recipient KIR ligand matching of unrelated donor hematopoietic stem cell transplantation was more beneficial to the total survival of patients. However, there was no significant difference in the recurrence of acute GVHD, and the mortality associated with transplantation, but this result may be affected by the degree of HLA coincidence, T cell removal and the characteristics of the disease itself.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R457.7
【共引文獻】
相關(guān)博士學位論文 前1條
1 姜波;K562-4-1BBL-MICA工程細胞構(gòu)建及其聯(lián)合IL-21對NK細胞體外擴增的研究[D];吉林大學;2014年
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