本文選題：紅細(xì)胞同種抗體 + 遲發(fā)型溶血性輸血反應(yīng)�。� 參考：《武漢大學(xué)》2014年博士論文

【摘要】：紅細(xì)胞同種抗體是引起臨床輸血不良事件及新生兒溶血病的直接原因,來源于獻(xiàn)血者或胎兒的外源性紅細(xì)胞抗原可刺激機(jī)體免疫系統(tǒng),使其產(chǎn)生針對外源性紅細(xì)胞抗原的同種抗體,而紅細(xì)胞同種抗-E抗體是臨床上最常見的抗體。 臨床對紅細(xì)胞同種抗體導(dǎo)致的輸血不良事件及新生兒溶血病往往在發(fā)生后才進(jìn)行治療,且易引起誤診或被忽略,影響了患者的臨床治療,甚至導(dǎo)致嚴(yán)重的后果。在臨床輸血實(shí)踐中,為預(yù)防此類事件的發(fā)生,國內(nèi)外僅有少數(shù)機(jī)構(gòu)對已產(chǎn)生紅細(xì)胞同種抗體的受血者進(jìn)行特異性抗原匹配輸血,但因?yàn)檫@種技術(shù)費(fèi)力、費(fèi)時、增加患者經(jīng)劑負(fù)擔(dān)且需要專業(yè)人才進(jìn)行操作,影響了其普及性；而對預(yù)防紅細(xì)胞同種抗-E抗體引起的新生兒溶血病目前尚無有效方法。針對上述不足,本研究旨在探討紅細(xì)胞同種抗-E抗體的形成機(jī)制,為臨床積極有效預(yù)防和治療該抗體引起的臨床輸血不良事件及新生兒溶血病提供科學(xué)依據(jù)。 第一部分紅細(xì)胞同種抗-E抗體引起輸血不良反應(yīng)及新生兒溶血病的風(fēng)險(xiǎn)及作用機(jī)制 研究目的： 通過調(diào)查漢族住院人群紅細(xì)胞同種抗體特異性、風(fēng)險(xiǎn)及流行情況,探討紅細(xì)胞同種抗-E抗體引起輸血不良反應(yīng)及新生兒溶血病的風(fēng)險(xiǎn)及機(jī)制。 研究方法： 利用微柱凝集技術(shù)對42517例漢族住院患者進(jìn)行了紅細(xì)胞同種抗體篩選。對抗體篩選陽性的患者標(biāo)本再用經(jīng)典試管法進(jìn)行紅細(xì)胞同種抗體特異性鑒定。同時收集抗體篩選陽性患者的臨床資料,如性別、年齡、輸血史、妊娠史、紅細(xì)胞同種抗體檢測記錄、輸血反應(yīng)及新生兒溶血病記錄等以分析抗體的發(fā)生率、特異性、風(fēng)險(xiǎn)及作用機(jī)制。 研究結(jié)果： 本研究在42517例住院患者中共檢測出212例帶有紅細(xì)胞同種抗體,紅細(xì)胞同種抗體總的發(fā)生率為0.50%,且在不同性別和年齡之間其發(fā)生率顯著不同。檢出抗體最多的依次為抗-E(87/212,41.0%)、抗-D(45/212,21.2%)、抗-M(41/212,19.3%)和抗-cE(13/212,6.1%)。在212例帶有紅細(xì)胞同種抗體患者中,共發(fā)現(xiàn)有17例嬰兒發(fā)生新生兒溶血病,其中13例由抗-D引起、3例由抗-E引起、1例由抗-Fya引起；另有4例患者在輸血后發(fā)生了遲發(fā)型溶血性輸血反應(yīng)。 研究結(jié)論： 在漢族住院人群中,紅細(xì)胞同種抗體總的發(fā)生率為0.50%,其中抗-E、抗-D和抗-M是最常見的抗體�？�-D和抗-E是引起新生兒溶血病或遲發(fā)型溶血性輸血反應(yīng)的主要風(fēng)險(xiǎn)因素。 第二部分紅細(xì)胞E抗原對E抗體產(chǎn)生的影響及風(fēng)險(xiǎn)評估 研究目的： 由于紅細(xì)胞同種抗-E抗體是最常見的有臨床意義的抗體,因此本研究主要探討外源紅細(xì)胞E抗原對紅細(xì)胞制品輸注患者同種抗-E抗體形成的影響及風(fēng)險(xiǎn)。 研究方法： 檢測1239例接受紅細(xì)胞制品輸注患者及1306例供血者紅細(xì)胞E抗原,并從1239例接受紅細(xì)胞制品輸注的患者中篩選出258例具有接受外源紅細(xì)胞E抗原刺激風(fēng)險(xiǎn)人群,監(jiān)測這些篩選人群在住院期間接受外源紅細(xì)胞E抗原刺激后的紅細(xì)胞同種抗-E抗體產(chǎn)生情況。 研究結(jié)果： 在隨機(jī)選取的接受紅細(xì)胞制品輸注人群中,約1/4的人群有接受外源紅細(xì)胞E抗原刺激的風(fēng)險(xiǎn)。在篩選出具有接受外源紅細(xì)胞E抗原刺激風(fēng)險(xiǎn)人群中,盡管約半數(shù)曾經(jīng)有輸血史和/或妊娠史,甚至其中30例曾經(jīng)有過多次輸血史和/或妊娠史,且其中12例在本次研究中又接受過多次外源紅細(xì)胞E抗原刺激,但本研究在這些人群中并未檢出紅細(xì)胞同種抗-E抗體或其他類紅細(xì)胞同種抗體。 研究結(jié)論： 接受紅細(xì)胞制品輸注人群具有較高接受外源紅細(xì)胞E抗原刺激的風(fēng)險(xiǎn),并且是啟動紅細(xì)胞同種抗-E抗體形成的機(jī)制之一,但不一定會產(chǎn)生紅細(xì)胞同種抗-E抗體。 第三部分免疫調(diào)節(jié)基因TRIM21對紅細(xì)胞同種抗-E抗體產(chǎn)生的影響及機(jī)理分析 研究目的： 通過分析紅細(xì)胞同種抗-E抗體產(chǎn)生患者不同性別、不同年齡間免疫調(diào)節(jié)基因TRIM21rs660位點(diǎn)變異情況及不同等位基因間細(xì)胞和體液免疫功能,探討該變異對紅細(xì)胞同種抗-E抗體產(chǎn)生的影響及機(jī)理。 研究方法： 通過基因測序的方法,檢測49例紅細(xì)胞同種抗-E抗體產(chǎn)生患者和35例未產(chǎn)生紅細(xì)胞同種抗-E抗體對照者TRIM21基因rs660位點(diǎn)變異情況,分析其等位基因在不同性別、不同年齡組間的分布情況,同時檢測了20例患者組和15例對照組人群不同等位基因間的細(xì)胞和體液免疫功能,并進(jìn)行比較分析,以探討其對紅細(xì)胞同種抗-E抗體產(chǎn)生的影響及機(jī)理。 研究結(jié)果： 在產(chǎn)生紅細(xì)胞同種抗-E抗體患者組中,攜帶有T等位基因的患者共有31例,攜帶有C等位基因的患者共有18例,TRIM21基因rs660位點(diǎn)不同等位基因在產(chǎn)生紅細(xì)胞同種抗-E抗體患者組不同性別之間分布差異無顯著性(P0.05)。在未產(chǎn)生紅細(xì)胞同種抗-E抗體對照組中,攜帶有T等位基因的患者共有26例,攜帶有C等位基因的患者共有9例,TRIM21基因rs660位點(diǎn)不同等位基因在未產(chǎn)生紅細(xì)胞同種抗-E抗體對照組不同性別之間分布差異無顯著性(P0.05)。在患者組和對照組之間,TRIM21基因rs660位點(diǎn)不同等位基因分布差異無顯著性(P0.05),而在不同性別間,TRIM21基因rs660位點(diǎn)不同等位基因的分布差異亦無顯著性(P0.05)。 在5歲年齡組中,T等位基因的患者共有9例,C等位基因的患者共有5例；5-10歲年齡組中,T等位基因的患者共有11例,C等位基因的患者共有5例；10歲年齡組中,T等位基因的患者共有13例,C等位基因的患者共有6例。經(jīng)對不同年齡組間TRIM21基因rs660位點(diǎn)不同等位基因的分布比較發(fā)現(xiàn),其在不同年齡組間的分布差異均無顯著性(P0.05)。 在患者組和對照組TRIM21基因rs660不同等位基因間,細(xì)胞和體液免疫功能差異均無顯著性(P0.05)。 研究結(jié)論： 在產(chǎn)生紅細(xì)胞同種抗-E抗體的患者人群和未產(chǎn)生紅細(xì)胞同種抗-E抗體的對照組人群,TRIM21基因rs660位點(diǎn)T等位基因頻率均高于C等位基因頻率。在不同的性別和年齡之間,TRIM2基因rs660位點(diǎn)等位基因的分布差異不存在顯著性。在TRIM21基因rs660不同等位基因間,研究人群細(xì)胞和體液免疫功能并無顯著性變化。本研究人群中,TRIN(?)21基因rs660位點(diǎn)變異不影響紅細(xì)胞同種抗-E抗體的產(chǎn)生。
[Abstract]:Erythrocyte homoantibody is the direct cause of the adverse events of clinical transfusion and hemolytic disease of the newborn. The exogenous erythrocyte antigen derived from the donor or fetus can stimulate the immune system and produce the homologous antibody against the exogenous erythrocyte antigen, and the erythrocyte homoisoanti -E antibody is the most common antibody in the clinic.
The adverse events of blood transfusion caused by erythrocyte homoisoantibody and the hemolytic disease of the newborn are often treated, and it is easy to cause misdiagnosis or neglect, which affects the clinical treatment of the patients and even causes serious consequences. In the practice of clinical transfusion, only a few institutions have produced to prevent this kind of thing from happening at home and abroad. The blood recipients of the erythrocyte homoantibody match the blood of the specific antigen to match the blood transfusion, but because this technique is difficult and time-consuming, it will increase the burden of the patient and need professional operation, which affects its popularity, and there is no effective method for preventing the hemolytic disease of the newborn caused by the erythrocyte homoisoanti -E antibody. The aim of this study is to explore the formation mechanism of erythrocyte isoanti -E antibody, and provide a scientific basis for the clinical active effective prevention and treatment of the adverse clinical transfusion events caused by the antibody and the hemolytic disease of the newborn.
Part one the risk and mechanism of transfusion induced adverse reactions and hemolytic disease of the newborn caused by -E antibody against red blood cells
The purpose of the study is:
By investigating the specificity, risk and prevalence of erythrocyte homograft antibodies in the Han population in the Han population, the risk and mechanism of erythrocyte allogeneic anti -E antibody caused by blood transfusion and hemolytic disease of the newborn were investigated.
Research methods:
Using the microcolumn agglutination technique, 42517 cases of Han hospitalized patients were screened for erythrocyte homograft antibody. The specific identification of erythrocyte homograft antibody was carried out by the classical test tube method. The clinical data of antibody screening positive patients, such as sex, age, blood transfusion history, pregnancy history, erythrocyte homohomoisoresistance, were collected. The incidence, specificity, risk and mechanism of antibody were analyzed by physical examination, blood transfusion reaction and neonatal hemolytic disease.
The results of the study:
In this study, 212 cases of erythrocyte homohomoantibody were detected in 42517 hospitalized patients. The total incidence of erythrocyte homoantibody was 0.50%, and the incidence of the antibody was significantly different between different sex and age. The highest detection antibodies were anti -E (87/212,41.0%), anti -D (45/ 212,21.2%), anti -M (41/212,19.3%) and -cE (13/212,6.1%). In 212 patients with erythrocyte homograft antibody, 17 cases of neonatal hemolytic disease were found, of which 13 were caused by anti -D, 3 were caused by anti -E, 1 were caused by anti -Fya, and 4 patients had delayed hemolytic transfusion after blood transfusion.
The conclusions are as follows:
In the Han population, the total incidence of erythrocyte homoisoantibodies is 0.50%, of which anti -E, anti -D and anti -M are the most common antibodies. Anti -D and anti -E are the main risk factors for neonatal hemolytic disease or delayed hemolytic transfusion reaction.
The second part is the influence of erythrocyte E antigen on the production of E antibody and its risk assessment.
The purpose of the study is:
Because erythrocyte isoanti -E antibody is the most common clinical antibody, this study mainly discusses the effect and risk of exogenous E antigen on the formation of allogeneic anti -E antibody in erythrocyte infusion patients.
Research methods:
The erythrocyte E antigen was detected in 1239 cases of erythrocyte infusion and 1306 cases of blood donors, and from 1239 patients receiving erythrocyte infusion, 258 patients with the risk of exogenous erythrocyte E antigen stimulation were screened, and these screening people were monitored to receive erythrocyte homohomoisoresistance after the external erythrocyte E antigen stimulation during hospitalization. The production of -E antibody.
The results of the study:
Among the randomly selected recipients of the transfusion of red cell products, about 1/4 of the population had a risk of receiving E antigen stimulation of the exogenous erythrocyte. Among the people who had been screened for the risk of E antigen stimulation with exogenous erythrocytes, about half of them had a history of blood transfusion and / or pregnancy history, and even 30 of them had had a history of multiple blood transfusions and / or pregnancy history, and In this study, 12 of the 12 cases received a number of exogenous erythrocyte antigen stimuli, but this study did not detect erythrocyte isoanti -E antibodies or other erythrocyte homograft antibodies.
The conclusions are as follows:
The population receiving erythrocyte infusion has a high risk of receiving the stimulation of the E antigen of the foreign red cell, and is one of the mechanisms to initiate the formation of the anti -E antibody of the red blood cell, but it does not necessarily produce the erythrocyte isoanti -E antibody.
The third part is the effect of immunomodulatory gene TRIM21 on the production of red blood cell homologous anti -E antibody and its mechanism.
The purpose of the study is:
The effect and mechanism of the mutation on the production of erythrocyte isoanti -E antibody were investigated by analyzing the variation of TRIM21rs660 loci in different ages and the cell and humoral immune function between different alleles by analyzing the sex of the erythrocyte isoanti -E antibody in different sex, the variation of the immunomodulatory gene in different ages and the immune function of different alleles.
Research methods:
The mutation of TRIM21 gene locus in 49 cases of erythrocyte isoanti -E antibody production and 35 cases of non erythrocyte isoanti -E antibody control was detected by gene sequencing, and the distribution of alleles in different sex and age groups was analyzed, and 20 patients and 15 control groups were detected at the same time. The cellular and humoral immune functions between the alleles were compared and analyzed to explore the effect and mechanism of its -E antibody production.
The results of the study:
There were 31 patients with T allele and 18 patients carrying C allele in the patients with erythrocyte allogeneic anti -E antibody. There was no significant difference between the different sex alleles of the TRIM21 gene rs660 loci in the group that produced the erythrocyte isoanti -E antibody group (P0.05). No red cell homohomoisoresistance was produced. In the -E antibody control group, there were 26 patients with T allele and 9 patients with C allele, and there was no significant difference in the distribution of TRIM21 gene rs660 alleles between different sex alleles of the erythrocyte allogeneic anti -E antibody control group (P0.05). The rs660 locus of TRIM21 gene between the patient group and the control group was between the patient group and the control group. There was no significant difference in the distribution of alleles in different alleles (P0.05), but there was no significant difference in the distribution of alleles at the rs660 locus of the TRIM21 gene in the same sex (P0.05).
In the age group of 5, there were 9 patients with T allele and 5 patients with C allele; 11 patients with T allele in 5-10 year old age group and 5 patients with C allele; 10 age group, T allele were 13, and C alleles were 6. The TRIM21 gene R between different age groups The distribution of alleles at s660 locus showed no significant difference among different age groups (P0.05).
There was no significant difference in cellular and humoral immune function between TRIM21 and rs660 alleles in patients and controls (P0.05).
The conclusions are as follows:
The frequency of the T allele of the TRIM21 gene rs660 loci was higher than the C allele frequency in the population of the patients who produced the erythrocyte homograft anti -E antibody and the anti -E antibody of the erythrocytes. The distribution difference of the TRIM2 gene rs660 loci allele was not significant between the different sex and age. The TRIM21 gene rs66 was not significant. The TRIM21 gene rs66 was not significant. There was no significant change in cell and humoral immune function between the 0 different alleles. The rs660 locus mutation of the TRIN (?) 21 gene did not affect the production of erythrocyte isoanti -E antibody in this study population.

【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R722.18;R457.1

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