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AECAs產(chǎn)生的致敏因素及其與腎移植術(shù)后不良事件的相關(guān)性分析

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【摘要】:目的:分析腎臟移植受者手術(shù)前AECAs陽(yáng)性的致敏因素,以及探究移植手術(shù)前預(yù)存的AECAs和移植手術(shù)以后新產(chǎn)生的AECAs對(duì)受者手術(shù)后半年內(nèi)移植腎臟功能恢復(fù)的影響。方法:第一部分,選取了2015年10月至2016年8月在解放軍第三0九醫(yī)院器官移植研究所等候欲行同種異體腎臟移植手術(shù)的85位病人為本部分的研究對(duì)象。留取病人手術(shù)前的血清,同時(shí)記錄病人的性別、年齡、體重指數(shù)、腎臟衰竭原因、替代支持治療類型及持續(xù)時(shí)間、手術(shù)前肌酐水平、移植史、妊娠史、輸血史等臨床資料。使用間接免疫熒光法(IIF)檢測(cè)病人血清中AECAs的表達(dá)情況,并根據(jù)結(jié)果將病人分為AECAs陽(yáng)性組和AECAs陰性組。檢測(cè)術(shù)前AECAs的陽(yáng)性率,分析術(shù)前致敏史對(duì)AECAs產(chǎn)生的影響。第二部分,以第一部分中已行同種異體腎臟移植手術(shù)的85位病人為本部分研究對(duì)象,留取受者術(shù)后1d、3d、7d、15d及1m各時(shí)間點(diǎn)血清,采用同第一部分的檢測(cè)方法檢測(cè)受者血清中AECAs的表達(dá)情況。同時(shí)采集受者術(shù)后半年內(nèi)各時(shí)間點(diǎn)的血清肌酐水平,并記錄DGF、排斥反應(yīng)、感染等事件的出現(xiàn)情況。依據(jù)檢測(cè)結(jié)果將患者分為3組:AECAs(Pre+/Post+)組、AECAs(Pre-/Post+)組和AECAs(Pre-/Post-)組,分析各組AECAs的表達(dá)與不良事件發(fā)生的相關(guān)性。應(yīng)用IBM SPSS Statistics 20統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行分析,計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差(Mean±SD)表示,計(jì)量資料之間的比較采用兩獨(dú)立樣本t檢驗(yàn)或采用單因素方差分析,計(jì)數(shù)資料之間比較采用χ2檢驗(yàn)、校正χ2檢驗(yàn)或Fisher確切概率檢驗(yàn),P0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:85位等候腎臟移植的病人中,有19位病人手術(shù)前外周血AECAs表達(dá)陽(yáng)性,陽(yáng)性率為22.4%。19位陽(yáng)性病人中,熒光模型出現(xiàn)3種類型:核周熒光斑塊型12例(63.2%),抗細(xì)胞骨架抗體型5例(26.3%),抗核抗體型2例(10.5%)。對(duì)AECAs陽(yáng)性組和AECAs陰性組進(jìn)行分析,兩組病人在性別、年紀(jì)、體重指數(shù)、替代支持治療類型及持續(xù)時(shí)間、手術(shù)前肌酐水平及原發(fā)性疾病等方面沒有統(tǒng)計(jì)學(xué)差異(P0.05)。在輸血、妊娠等單獨(dú)的致敏因素影響下,兩組病人仍沒有統(tǒng)計(jì)學(xué)差異(P=0.37;P=0.34)。按致敏史將病人分為致敏組(既往有輸血或妊娠史)和非致敏組(既往無(wú)輸血和妊娠史),致敏組病人28位,其中AECAs陽(yáng)性病人10位(35.7%),非致敏組病人57位,其中AECAs陽(yáng)性病人9位(15.8%),既往有致敏經(jīng)歷的患者AECAs陽(yáng)性率顯著高于無(wú)致敏經(jīng)歷的患者,兩組病人之間存在有明顯的統(tǒng)計(jì)學(xué)差異(χ2=4.295,P=0.038)。85位病人均在我院行同種異體腎臟移植手術(shù),手術(shù)前19位AECAs陽(yáng)性病人在手術(shù)后各時(shí)間點(diǎn)檢測(cè)均為陽(yáng)性,術(shù)前66位AECAs陰性病人在術(shù)后各時(shí)間點(diǎn)檢測(cè)時(shí)有10位病人出現(xiàn)AECAs轉(zhuǎn)陽(yáng),其余56位病人手術(shù)前及手術(shù)后各時(shí)間點(diǎn)檢測(cè)AECAs均為陰性。10位AECAs(Pre-/Post+)患者中,3位病人于手術(shù)后的第2-3d出現(xiàn)AECAs,2位病人于手術(shù)后的第4-7d出現(xiàn)AECAs,5位病人于手術(shù)后的第8-15d出現(xiàn)AECAs。對(duì)AECAs(Pre+/Post+)組、AECAs(Pre-/Post+)組和AECAs(Pre-/Post-)組進(jìn)行比較,3組病人在性別、年齡、體重指數(shù)、替代支持治療類型及持續(xù)時(shí)間、原發(fā)性疾病方面都沒有統(tǒng)計(jì)學(xué)差異(P0.05)。對(duì)應(yīng)的供者類型、性別、年齡、體重指數(shù)和供腎的冷缺血時(shí)間等也沒有統(tǒng)計(jì)學(xué)差異(P0.05)。在術(shù)前誘導(dǎo)方案的應(yīng)用及術(shù)后免疫抑制維持治療方案上,3組也不存在統(tǒng)計(jì)學(xué)差異(P0.05)。AECAs(Pre-/Post+)組排斥反應(yīng)的發(fā)生率較其他兩組高,AECAs(Pre-/Post+)30%vs AECAs(Pre+/Post+)5.3%vs AECAs(Pre-/Post-)17.9%,但未達(dá)到統(tǒng)計(jì)學(xué)差異(P=0.21)。術(shù)后感染的發(fā)生情況在3組患者中也沒有統(tǒng)計(jì)學(xué)差異(P=0.31)。但在AECAs(Pre-/Post+)組DGF的發(fā)生率(70%)及持續(xù)時(shí)間(54±42.5d)均明顯高于其他兩組,差異存在統(tǒng)計(jì)學(xué)意義(P0.05),并且在腎移植術(shù)后1周(P=0.02)、1月(P=0.04)、3月(P=0.01)、6月(P=0.02)時(shí)AECAs(Pre-/Post+)組肌酐水平均高于其他兩組,差異存在統(tǒng)計(jì)學(xué)意義。結(jié)論:本次研究結(jié)果表明(1)術(shù)前有移植、輸血、妊娠等致敏史的患者AECAs的陽(yáng)性率會(huì)明顯增加,且陽(yáng)性結(jié)果類型主要為核周熒光斑塊型、抗細(xì)胞骨架抗體型和抗核抗體型3種。(2)手術(shù)后新產(chǎn)生的AECAs能夠增加腎移植手術(shù)后移植腎功能延遲恢復(fù)(DGF)的發(fā)生風(fēng)險(xiǎn),延長(zhǎng)DGF持續(xù)時(shí)間,影響手術(shù)后半年內(nèi)移植腎功能的恢復(fù)。
[Abstract]:Objective: To analyze the sensitization factors of AECAs positive in renal transplant recipients, and to explore the effect of new AECAs on renal function recovery in the first half of the operation of the recipient after the pre-stored AECAs and the transplant operation. Methods: The first part, from October 2015 to August 2016, was selected for the study of 85 patients at the Institute of Organ Transplantation in the third 0-9 hospital of the People's Liberation Army (PLA) for the purpose of this part. Clinical data such as sex, age, body weight index, kidney failure reason, alternative support treatment type and duration, pre-operative myocardiac level, transplant history, pregnancy history, and blood transfusion history were recorded. The expression of AECAs in serum of patients was detected by indirect immunofluorescence (IIF), and the patients were divided into AECAs positive group and AECAs negative group according to the results. The positive rate of AECAs before operation was detected, and the effect of preoperative sensitization history on AECAs was analyzed. In the second part,85 patients with the same allogenic kidney transplantation in the first part were the subject of the partial study, and the serum levels of AECAs in the recipient's serum were detected by the detection method of the same first part. At the same time, the level of serum myoglobin in each time point within six months of the recipient was collected, and the occurrence of the events such as DGF, rejection and infection was recorded. The patients were divided into three groups: AECAs (Pre +/ Post +) group, AECAs (Pre-/ Post +) group and AECAs (Pre-/ Post-) group according to the detection results, and the correlation between the expression of AECAs and the adverse events was analyzed. The data is analyzed by using the statistical software of the IBM SPSS Statistics 20. The mean square standard deviation (Mean-SD) is used for the measurement data. The two independent samples t are used for the comparison between the measurement data and the one-factor analysis of variance is adopted. The correction factor 2 test or the Fisher's exact probability test, P0.05, indicates that the difference is of statistical significance. Results: The expression of AECAs in the peripheral blood of 85 patients with renal transplantation was positive, and the positive rate was 22.4%. Among the 19 positive patients,3 types were observed in the fluorescence model:12 (63.2%) of the nuclear-week fluorescent plaque and 5 (26.3%) of the anti-cytoskeleton antibody. 2 cases of anti-nuclear antibody (10.5%). The positive group of AECAs and the negative group of AECAs were analyzed, and there was no statistical difference between the two groups in terms of sex, age, body weight index, alternative support treatment type and duration, pre-operative myocardiac level and primary disease (P0.05). There was no statistical difference between the two groups (P = 0.37; P = 0.34) under the influence of individual sensitization factors such as blood transfusion, pregnancy and the like. The patient was divided into a sensitizing group (with a history of blood transfusion or pregnancy) and a non-sensitizing group (a history of no previous blood transfusion or pregnancy) and a non-sensitizing group (prior to the history of no blood transfusion and pregnancy) according to the sensitive history, with 28 patients in the sensitization group, of which 10 (35.7%) of the AEAs-positive patients and 57 in the non-sensitizing group, of which 9 (15.8%) of the AECAs-positive patients, The positive rate of AECAs in patients with prior sensitization was significantly higher than those with no sensitization, and there was a significant difference between the two groups (Sup2 = 4.295, P = 0.038). The 19 AECAs positive patients were positive at all time after the operation, and the patients with AECAs were positive at all time points after operation, and there were 10 patients with AECAs turned positive at each time point after operation. AECAs were detected in the remaining 56 patients before and after operation and at all time points after the operation. In the 10 AECAs (Pre-/ Post +) patients,3 patients had AECAs in the second to third day after the operation, and 2 patients had AECAs on the 4th to 7th day after the operation, and the 5 patients had AECAs on the 8th to 15th day after the operation. Compared with the AECAs (Pre-/ Post +) group, AECAs (Pre-/ Post +) group and AECAs (Pre-/ Post-) group, there was no statistical difference in the three groups in terms of sex, age, body weight index, alternative support treatment type and duration, and primary disease (P0.05). There was no statistical difference between the corresponding donor type, sex, age, body weight index and cold ischemia time for the kidney (P0.05). There was no statistical difference in 3 groups (P0.05). The rate of rejection of AECAs (Pre-/ Post +) group was higher than that of other two groups, and the rate of AECAs (Pre-/ Post +)30% vs. AECAs (Pre +/ Post +) 5.3% vs. AECAs (Pre-/ Post-) was 17.9%, but no statistical difference was achieved (P = 0.21). The incidence of post-operative infection was also not statistically different in the 3 patients (P = 0.31). However, the incidence of DGF (70%) and duration (54-42.5 d) in the AECAs (Pre-/ Post +) group were significantly higher than those in the other two groups (P = 0.02),1 month (P = 0.04),3 months (P = 0.01), and 6 months (P = 0.02), and the level of the APCs (Pre-/ Post +) group was higher than that of the other two groups. There was a statistically significant difference in the difference. Conclusion: The results of this study show that (1) The positive rate of AECAs in patients with pre-operation, transfusion, pregnancy and so on is significantly increased, and the positive result type is mainly the nuclear-week fluorescent plaque type, the anti-cytoskeleton antibody type and the anti-nuclear antibody type 3. (2) The newly-generated AECAs after operation can increase the risk of delayed recovery of renal function after renal transplantation (DGF), prolong the duration of DGF, and affect the recovery of transplanted kidney function within half a year after operation.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R699.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 金茜;杜博;孫文英;李興庫(kù);;抗內(nèi)皮細(xì)胞抗體在腎移植慢性排斥反應(yīng)中的作用[J];國(guó)際免疫學(xué)雜志;2013年01期

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