HLA-Cw基因的高分辨分型在造血干细胞移植中意义的初步探讨  

Investigation on high resolution matching of HLA-Cw and effect on unrelated blood stem cell transplantation in acute leukemia

作　　者：何军[1] 陈子兴[1] 侯建全[1] 吴德沛[1] 鲍晓晶[1] 姚利[1] 袁晓妮[1] 岑建农[1] 邱桥成[1] 狄文英 张辉[2] 张健[2] 徐惠新[2] 

机构地区：[1]苏州大学附属第一医院江苏省血液研究所,中国造血干细胞捐献者资料库HLA高分辨配型定点实验室,215006 [2]苏州市红十字中心血站

出　　处：《中华微生物学和免疫学杂志》2007年第7期643-646,共4页Chinese Journal of Microbiology and Immunology

基　　金：卫生部科研基金(wkj2006-2-023);江苏省卫生厅135开放项目(K0611);江苏省高校自然基金(07KJB320106)

摘　　要：目的研究HLA-Cw基因的高分辨分型在急性白血病非亲缘性造血干细胞移植中的意义。方法对中国造血干细胞捐献者资料库中提供的76例白血病患者(ALL 21例、CML 32例、AML 23例),采用序列特异性引物聚合酶链反应(PCR-SSP)联合序列特异性寡核苷酸探针(PCR-SSOP)方法进行HLA高分辨分型。结果ALL患者中HLA-Cw高分辨分型的常见位点:Cw*0102、Cw*0304、Cw *0302、Cw*0702、Cw*0801;表型频率分别为0.57、0.33、0.19、0.14、0.14。ALL患者与志愿者相比其Cw*0102、Cw*0304的表型频率差异有统计学意义,P<0.05;而Cw*0302、Cw*0702、Cw*0801的表型频率无统计学意义,P>0.05。7例ALL患者与供者HLIA的10个位点全相合,占33.3%,HLA-Cw全相合最常见的基因亚位点为Cw*0102(4/7),次之为Cw*0702(2/7)。CML患者中HLA-Cw高分辨分型的常见位点:Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0401、Cw*0303;表型频率分别为0.41、0.34、0.22、0.19、0.16、0.13,这些基因位点与志愿者相比其表型频率均无统计学意义,P>0.05。8例患者与供者的10个位点全相合,占25.0%,HLA-Cw全相合最常见的基因亚位点为Cw*0702(5/8),次之为Cw*0304(3/8)。在23例AML患者中4例与供者HLA的10个位点全相合患者均为M_2型。结论在ALL患者中其Cw*0102和Cw*0304基因表型频率明显增高,有利于ALL患者寻找到相合位点的供体。HLA-Cw基因是造成移植物抗宿主病(GVHD)发生和影响移植效果的重要因素,在非亲缘性和单倍体移植中必须进行HLA-Cw基因的高分辨检测。Objective To study high resolution typing of HLA-Cw and its effect on unrelated blood stem cell transplantation（BMT） in acute leukeamia. Methods High resolution HLA-Cw analysis was performed in 76 patients（ALL 21 eases, CML32 eases, AML 23 eases） from the data base of China Marrow Donor Program by PCR-SSP and PCR-SSOP. Results In ALL patients, the HLA=Cw variants with common gene site were Cw ＊ 0102, Cw ＊ 0304, Cw ＊ 0302, Cw ＊ 0702 and Cw ＊ 0801 ; the phenotype frequencies were 0.57, 0.33, 0.19, 0.14 and 0.14. The differences between these phenotype frequeneies of Cw ＊ 0102 and Cw ＊ 0304 were statistically significant in ALL and donors（ P 〈 0.05）, but no significance difference between these phenotype frequencies of Cw ＊ 0302, Cw ＊ 0702 and Cw ＊ 0801 （ P 〉 0.05）. Seven ALL patients（ 7/21 ） and donors had matched loci in HLA-A, B, Cw, DRB1 and DQB1, among which Cw ＊ 0102 was the subsite with highest frequency, the second one was Cw ＊ 0702. In CML patients, the HLA-Cw variants with common gene site were Cw ＊ 0702, Cw ＊ 0102, Cw ＊ 0304, Cw ＊ 0801, Cw ＊ 0401 and Cw ＊ 0303 ; the phenotype frequencies were 0.41, 0.34, 0.22, 0.19, 0.16 and 0.13, the differences between these phenotype frequencies were not significant（ P 〉 0.05）. Eight CML patients（8/32） and donors had matched loci in HLA-A, B, Cw, DRB1 and DQB1, among which Cw ＊ 0702 was the subsites with highest frequency, the second one was Cw ＊ 0304. All of the four M2 patients and donors had prefectly matched loci in 23 eases of AML . Conclusion Cw ＊ 0102 and Cw ＊ 0304 have the obviously highest phenotype frequency in ALL and more easily should be searched matched donor. As the HLA-Cw plays important role in GVHD occurrence and the effect of BMT, more attention should be paid to HLA-Cw allele in unrelated and haploid BMT.

关 键 词：HLA-CW 高分辨分型 造血干细胞移植 白血病 

分 类 号：R733.7[医药卫生—肿瘤]