CAJ | 학술논문

目的探讨不同激活性杀伤细胞免疫球蛋白样受体(KIR)在人类白细胞抗原(HLA)全相合无关供体异基因造血干细胞移植中的作用.方法采用序列特异性引物聚合酶链反应(PCR-SSP)和基因测序(SBT)方法,对中国造血干细胞捐献者资料库中提供的74对HLA全相合供受者进行KIR及HLA高分辨分型,其中38例进行异基因造血干细胞移植,接受移植的患者FAB分型为急性淋巴细胞白血病(ALL) 18例、慢性粒细胞白血病( CML8)例、急性髓系白血病(AML) 12例,检测供受者中KIR2DS4、KIR2DS1、KIR3DS1、KIR2DS5、KIR2DS2和KIR2DS3基因的比例,并采用Kaplan-Meier法,对KIR2DS4亚型与移植术后患者的生存率进行统计学分析.结果在74对供受者中100.00％有KIR2DS4基因,64.87％ (48/74)有KIR2DS1基因,60.81％(45/74)有KIR3DS1基因,45.95％(34/74)有KIR2DS5基因,44.60％(33/74)有KIR2DS2基因,35.14％(26/74)有KIR2DS3基因.在AML和CML分型的移植中供者有激活性KIR2DS1、KIR2DS3和KIR3DS1基因高表达；而在ALL分型的移植中低表达.在表达KIR2DS4的供受者中,其中51.40％(38/74)仅表达2DS4*001/002亚型,23.60％(18/74)仅表达2DS4*003-007亚型,25.00％(19/74)为两种亚型同时表达.供受者仅有2DS4*001/002亚型的病例均在移植后死亡;供者具有2DS4*003-007亚型的病例1年无病生存率为83.30％(5/6).当供者aKIR基因数目≥3个时,ALL患者的1年无病生存率为87.50％ (7/8);当供者aKIR基因数目＜3个时,AML/CML患者1年无病生存率为83.33％ (5/6).结论在无关供体异基因造血干细胞移植中,KIR单体型A、激活性KIR受体基因亚型和数目的差异表达,对降低GVHD的发生和移植的预后起关键作用.
목적 탐토불동격활성살상세포면역구단백양수체(KIR)재인류백세포항원(HLA)전상합무관공체이기인조혈간세포이식중적작용.방법 채용서렬특이성인물취합매련반응(PCR-SSP)화기인측서(SBT)방법,대중국조혈간세포연헌자자료고중제공적74대HLA전상합공수자진행KIR급HLA고분변분형,기중38례진행이기인조혈간세포이식,접수이식적환자FAB분형위급성림파세포백혈병(ALL) 18례、만성립세포백혈병( CML8)례、급성수계백혈병(AML) 12례,검측공수자중KIR2DS4、KIR2DS1、KIR3DS1、KIR2DS5、KIR2DS2화KIR2DS3기인적비례,병채용Kaplan-Meier법,대KIR2DS4아형여이식술후환자적생존솔진행통계학분석.결과 재74대공수자중100.00％유KIR2DS4기인,64.87％ (48/74)유KIR2DS1기인,60.81％(45/74)유KIR3DS1기인,45.95％(34/74)유KIR2DS5기인,44.60％(33/74)유KIR2DS2기인,35.14％(26/74)유KIR2DS3기인.재AML화CML분형적이식중공자유격활성KIR2DS1、KIR2DS3화KIR3DS1기인고표체；이재ALL분형적이식중저표체.재표체KIR2DS4적공수자중,기중51.40％(38/74)부표체2DS4*001/002아형,23.60％(18/74)부표체2DS4*003-007아형,25.00％(19/74)위량충아형동시표체.공수자부유2DS4*001/002아형적병례균재이식후사망;공자구유2DS4*003-007아형적병례1년무병생존솔위83.30％(5/6).당공자aKIR기인수목≥3개시,ALL환자적1년무병생존솔위87.50％ (7/8);당공자aKIR기인수목＜3개시,AML/CML환자1년무병생존솔위83.33％ (5/6).결론 재무관공체이기인조혈간세포이식중,KIR단체형A、격활성KIR수체기인아형화수목적차이표체,대강저GVHD적발생화이식적예후기관건작용.
Objective To explore the impact of different activating KIRs in HLA matched unrelated allo-hematopoietic stem cell transplantation.Methods The HLA/KIR genotypes of 74 patients and their matched unrelated donors from database of CMDP were determined by PCR-SSP and SBT.38 patients received unrelated allo-HSCT.Among them,18 were ALL,8 were CML and 12 were AML by FAB typing.The survival of recipients with aKIR subtyping was analyzed using Kaplan-Meier after allo-HSCT.Results The frequencies of KIR2DS4,KIR2DS1,KIR3DS1,KIR2DS5,KIR2DS2 and KIR2DS3 were 100.00％,64.87％(48/74),60.81％ (45/74),45.95 ％ (34/74),44.6 ％ ( 33/74 ),and 35.14 ％ (26/74) respectively in 74 pairs of donor-recipient.Frequencies of activating KIR2DS1,KIR 2DS3 and KIR 3DS1 genotypes were high in donors of AML and CML groups,but low in ALL group.The frequencies of KIR2DS4*001/002 and 2DS4*003-007 homozygotes were 51.40 ％ (38/74) and 23.60 ％(18/74) respectively,while the frequency for 2DS4*00/1/002 and 2DS4*003-007 heterozygote was 25.00 ％ ( 19/74).The mortality rate of patient and donor with KIR2DS4*001-002 allele was 100 ％.The one-year disease-free survival (DFS) of recipients receiving stem cells from donor with 2DS4*003-007 allele was 83.30％ (5/6).When the donors have three or more aKIR,one-year DFS was 87.50 ％ (7/8) in ALL group.But for AML/CML,it was 83.33 ％(5/6) if the donor had one or two aKIR.Conclusion The KIR genotyping in haplotype A and the differential expression of the number and subtype in aKIR may be related to the reduced occurrence of aGVHD and better clinical outcome in unrelated A11o-HSCT.