汉族健康人群KIR分布对异基因造血干细胞移植供者选择的影响

目的探讨杀伤细胞免疫球蛋白样受体（KIR）在中国人群中的分布规律及其对异基因造血干细胞移植供者选择的影响。方法采用序列特异性引物PCR（PCR-SSP）分型技术检测了79例汉族人群中KIR的基因型分布、74例异基因造血干细胞移植供受者对KIR及HLA基因型。结果KIR2DL1的基因分布频率为100％,KIR2DL2为20％,KIR2DL3为100％,KIR3DLI为94．81％。95．9％的供者携带与异基因造血干细胞移植关系密切的三组KIR受体。结论汉族人群具有独特的KIR分布规律,KIR2DL1、KIR3DL1是在中国人群异基因造血干细胞移植中起主要作用的KIR受体。     

异基因造血干细胞移植治疗Fms样酪氨酸激酶3基因内部串联重复(FLT3-ITD)阳性的急性髓性白血病的疗效分析

 目的 分析异基因造血干细胞移植(allo-HSCT)治疗伴有Fms样酪氨酸激酶3基因内部串联重复(FLT3-ITD)阳性的急性髓性白血病(AML)的疗效,探讨不同移植方式及疾病状态对该类患者预后的影响。方法 2006年10月至2012年10月在苏州大学附属第一医院行allo-HSCT的AML患者共314例,其中FLT3-ITD阳性54例,回顾性分析allo-HSCT对FLT3-ITD阳性AML患者的临床疗效。结果 54例FLT3-ITD阳性患者3年总生存(OS)率为56%, 3年无白血病生存(LFS)率为47%。其中同胞人类白细胞抗原(HLA)全相合及亲缘HLA单倍型相合造血干细胞移植的患者3年OS率分别为56%和60%,3年LFS率为45%和54%。两组在OS时间及LFS时间方面的差异均无统计学意义(χ²=0.074,P=0.786; χ²=0.006,P=0.941)。47例(87.0%)患者移植前本病处于首次完全缓解(CR1),7例(13.0%)患者移植前本病处于非CR1期。处于CR1期的患者的生存显著优于非CR1期患者。结论 allo-HSCT是FLT3-ITD阳性AML患者的有效治疗方法,亲缘HLA单倍型相合造血干细胞移植与同胞HLA全相合移植疗效相似。疾病复发是影响其疗效的主要因素。
        

移植前及预处理期间肝功能异常对异基因造血干细胞移植效果的影响

 目的 探讨异基因造血干细胞移植(allo-HSCT)患者移植前和预处理期间肝功能异常的特征及其与肝脏合并症和预后的关系。方法 回顾性分析196例allo-HSCT治疗血液系统疾病患者,采集其移植前和预处理期间肝功能数据,观察其对造血重建、移植相关肝脏并发症、生存和移植相关死亡的影响。结果 196例患者中,38例移植前存在肝功能异常,159例预处理期间发生肝功能异常,28例(17.6%)出现3度肝损害,无4度肝损害出现。移植前和预处理期间肝功能异常对造血重建时间、肝静脉阻塞病(HVOD)、肝脏急性移植物抗宿主病(aGVHD)和慢性移植物抗宿主病(cGVHD)发生无显著影响。单因素分析显示年龄(P=0.022)、移植前疾病状态高危(P=0.003)、移植前AST(P=0.019)和TBil水平升高(P=0.015)、Ⅲ~Ⅳ度肝脏aGVHD(P=0.000)和HVOD(P=0.000)是影响总生存(OS)率的危险因素。多因素Cox回归分析显示移植前疾病状态为高危(P=0.002)、Ⅲ~Ⅳ度肝脏aGVHD(P=0.000)是影响OS率的独立危险因素,同时也是影响移植相关死亡(TRM)率的独立危险因素(P值分别为0.002和0.000),而移植前和预处理期间肝功能异常对OS率和TRM率无显著影响。结论 1~2度肝功能异常患者,在密切监测肝功能、充分保肝治疗及积极预防HVOD基础上,可考虑进行allo-HSCT。
        

供者巨细胞病毒血清学阴性状态对异基因造血干细胞移植患者预后影响的临床分析

目的:研究巨细胞病毒（CMV）血清学阴性供者对CMV血清学阳性患者移植预后的影响。方法:回顾性分析2013年3月至2020年3月在北京大学人民医院血液科接受CMV血清学阴性供者（CMV IgG阴性）移植物的16例行异基因造血干细胞移植的恶性血液肿瘤患者,定义为CMV血清学阴性供者组（D -/R ...     

成人人类白细胞抗原全相合与不相合造血干细胞移植后急性移植物抗宿主病的临床特点与预后

 目的 比较成人人类白细胞抗原(HLA)全相合与HLA不相合异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)的临床特点与疗效。方法 回顾性分析2010年1月至2011年12月于北京大学血液病研究所进行亲缘allo-HSCT患者的临床病历资料,分析不同类型移植后aGVHD的发病类型与特点以及临床疗效的差异。结果 544例患者中,HLA不相合移植后的aGVHD发生率为50.2%,明显高于HLA全相合移植(20.4%,P<0.001),且发生得更早,但Ⅲ°~Ⅳ° aGVHD的累积发生率两组之间差异并无统计学意义(4.5%比6.8%, P=0.066);全相合移植中肠道aGVHD发生率较高(31.1%),而在不相合移植中以皮肤aGVHD为主(66.5%),肠道和肝脏aGVHD发生率均较全相合移植低;全相合移植发生aGVHD时发热患者比例较不相合移植低(28.9% 比47.6%,P=0.028);全相合移植与不相合移植相比,aGVHD总体治愈率低,特别是Ⅲ°~Ⅳ° aGVHD最终疗效差,二线治疗后的完全缓解率低于不相合移植(88.9%比98.8%,P=0.006),aGVHD相关病死率高于不相合移植(11.1%比2.4%,P=0.024)。结论 HLA不相合移植后aGVHD发生率明显高于全相合患者,但重度aGVHD发生率两组间差异无统计学意义,两组患者一线治疗缓解率相近,但HLA不相合移植患者二线治疗后aGVHD总体缓解率更高。     

急性移植物抗宿主病患者发生移植相关血栓性微血管病的危险因素及预后分析

  目的 探讨急性移植物抗宿主病（aGVHD）患者中移植相关血栓性微血管病（TA-TMA）发生的危险因素和影响TA-TMA预后的因素。方法 选取356例在北京大学血液病研究所接受异基因造血干细胞移植后发生aGVHD的患者为研究人群,选取33例移植后发生TA-TMA的患者作为病例组,以危险集抽样的方法在同一队列中随机选取年龄和随访时间匹配的患者组成对照组（77例）。比较两组间的危险因素和预后情况。结果 TA-TMA的中位发生时间为移植后3.5（1.2~23.0）个月。TA-TMA发病距aGVHD诊断的中位时间为25（7~257）d。aGVHD发生时间、起始严重程度、一线治疗失败及二线治疗中使用他克莫司与aGVHD患者发生TA-TMA独立相关,具有2种以上危险因素的患者TA-TMA风险明显升高（OR=210.0,P=0.000）。22例（66.7%）TA-TMA患者死亡,而进展型TA-TMA是预后的惟一不良影响因素。各种治疗方法均不能改善TA-TMA患者的预后。结论 aGVHD的多种特点与TA-TMA相关,便于筛选出aGVHD合并TA-TMA的高危患者,并指导选择更合理的治疗方案。        

造血基质细胞与造血干细胞移植

基质细胞是造血微环境的主要成分,对造血起不可缺少的调节和支持作用。造血干细胞移植患者的骨髓基质细胞会受一以不同程度损害,供体基抽细胞移植作为造血干细胞移植的辅助治疗可改善受体造血微环境,突破异基因移植的主要组织相容性复合物（MHC）限制,从而提高造血干细胞移植成功率。     

山东地区汉族人群KIR基因多态性分析

目的 分析山东地区汉族人群杀伤细胞免疫球蛋白样受体(KIR)基因多态性及基因型和单倍型多态性,为进一步研究KIRs与疾病的关系奠定基础.方法 采用序列特异性引物PCR法(PCR-SSP)对412例山东地区无血缘关系的汉族健康志愿者进行KIR基因频率检测及基因型和单倍型分析.结果 ①KIR基因频率:可检测到目前已知的18种KIR基因;所有个体均检测到3个框架基因(2D14、3DL2、3D13)以及KIRZ,其基因频率均为100%.3DP1、2DL3、2DL1、3DL1和2DS4基因较为常见,频率分别为99.03%、98.79%、98.79%、98.79%、96.84%;而2DL2、2DS2、3DP1v基因频率较低.②KIR基因型频率:共检出基因型28种,以AJ(2,2)、AF(1,2)型最常见,其次为AH(5,2)、G(4,5)、M(1,5);另外有11种基因型在自人中尚未见报道.③KIR基因单倍型频率:共检出单倍型16种,最常见的是单倍型2,频率为46.36%;其次为单倍型1,频率为25.61%.结论 山东地区汉族人群有其独特的KIRs基因频率、基因型频率和单倍型频率分布;本研究可为进一步研究KIRs与疾病的相关性提供依据.     

异基因造血干细胞移植中巨细胞病毒潜伏感染的防治

目的:观察依据异基因造血干细胞移植前受者巨细胞病毒(CMV)血清学检测结果采取不同的CMV感染防治方案的临床效果。方法:行异基因造血干细胞移植的37例患者,移植预处理前1周依据受者CMV血清学检测结果,对于移植前PP65抗原、CMV抗体及CMV-DNA定量均阴性的受者,应用阿昔洛韦预防CMV感染;移植前PP65、IgM抗体及DNA定量阴性,IgG抗体阳性的受者应用静脉更昔洛韦预防CMV感染。预处理中及移植后均采用阿昔洛韦进行病毒感染的预防,并定期检测PP65及CMV-IgM和CMV-DNA定量,当出现PP65阳性和/或CMV-IgM阳性、病毒复制增加时,给予更昔洛韦或膦甲酸钠联合人免疫球蛋白治疗。结果:36例受者移植后检测CMV抗体IgG均为阳性,巨细胞病毒血症占18.9%(7/37),CMV病占10.8%(4/37),CMV感染的时间为移植后+27～+65d,CMV感染多见于非血缘、HLA不全相合及发生aGVHD的患者,经更昔洛韦和或膦甲酸钠治疗后无一例因CMV病死亡。应用不同预防CMV感染方法的患者间造血重建时间无明显差异。结论:依据受移植前受者血清学检测结果给予不同的预防方案并结合预先治疗方案防治CMV感染可以明显减少CMV潜伏感染转变为CMV病的概率,且对造血重建无影响。     

异基因造血干细胞移植后巨细胞病毒感染的预先治疗

目的:探讨预防治疗及预先治疗对异基因造血干细胞移植后CMV感染的干预作用.方法:225例异基因造血干细胞移植患者中160例接受预先治疗,65例接受预防治疗,用logistic回归模型分析影响CMV感染的危险因素.结果:预先治疗组与预防治疗组比较,CMVpp65抗原血症、CMV病和CMV病死亡率分别为28.1%(35.3%,P>0.05),1.9%(12.3%,P<0.05)和0.6%(10.7%,P<0.01).单倍体相合移植组出现CM-Vpp65血症33.0%(40.0%,P>0.05)、CMV病发生率1.9%(12.0%,P<0.05)、死亡率0.0%(10.0%,P<0.05),均低于相合移植.单倍体相合移植组中CMVpp65阳性发生的主要危险因素为重症GVHD、移植前给予抗CMV治疗以及是否混合其他严重感染.结论:异基因移植后预先治疗优于预防治疗,可以明显减低CMV病的发生和死亡.     

Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Licensed natural killer (NK) cells have been demonstrated to have anti‐cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor‐recipient pairs and the killer cell immunoglobulin–like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post‐T‐cell‐replete haploidentical stem cell transplantation. Multivariate analysis showed that donor‐recipient KIR ligand graft‐versus‐host or host‐versus‐graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377–4·744, P = 0·003) post‐transplantation. Donor‐recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post‐transplantation. In addition, the percentage of γ‐interferon expression on donor‐derived NK cells was significantly higher in the recipients among the recipient‐donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft‐versus‐host or host‐versus‐graft direction mismatch on days 30 and 100 post‐transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor‐recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell‐mediated protection against CMV reactivation.     

Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia

Survival for patients with acute myeloid leukemia (AML) is limited by treatment-related mortality (TRM) and relapse after unrelated donor (URD) hematopoietic cell transplantation (HCT). Natural killer (NK)-cell alloreactivity, determined by donor killer-cell immunoglobulin-like receptors (KIRs) and recipient HLA, correlates with successful HCT for AML. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: at least 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 209 HLA-matched and 239 mismatched T-replete URD transplantations for AML. Three-year overall survival was significantly higher after transplantation from a KIR B/x donor (31% [95% CI: 26-36] vs 20% [95% CI: 13-27]; P = .007). Multivariate analysis demonstrated a 30% improvement in the relative risk of relapse-free survival with B/x donors compared with A/A donors (RR: 0.70 [95% CI: 0.55-0.88]; P = .002). B/x donors were associated with a higher incidence of chronic graft-versus-host disease (GVHD; RR: 1.51 [95% CI: 1.01-2.18]; P = .03), but not of acute GVHD, relapse, or TRM. This analysis demonstrates that unrelated donors with KIR B haplotypes confer significant survival benefit to patients undergoing T-replete HCT for AML. KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes.     

Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation

We performed a retrospective cohort study to find out whether the use of reduced‐intensity conditioning (RIC) might reduce the risk of early death from pneumonia. Pneumonia‐associated deaths were evaluated in 691 hematopoietic stem cell transplantation (HSCT) patients. The majority had a hematological malignancy (n = 504) and an HLA‐matched donor (n = 584). RIC was given to 336 patients and myeloablative conditioning (MAC) to 355. Data concerning radiology, culture and autopsy results were evaluated together with risk factors for death related to pneumonia within or after 100 d after HSCT (early and overall pneumonia). In 60 patients, pneumonia contributed to death (early n = 17). The cumulative incidence of early pneumonia‐related death was 2.8% and 2.1% in MAC and RIC patients, respectively. The cumulative incidence of overall pneumonia‐related death was 8.2% and 10.5%, respectively. In 40 patients, (67%) an etiology could be established, with 19 patients having proven or probable mold infection. In the multivariate analyses, acute graft‐versus‐host disease (GVHD) grades II–IV, cytomegalovirus (CMV) infection and having received mesenchymal stromal cells (MSCs) were factors associated with overall pneumonia‐related death. Bacteremia and a previous HSCT were associated with early pneumonia‐related death. RIC did not reduce the incidence of early death associated with pneumonia. Acute GVHD II–IV, CMV infection and MSC treatment were factors associated with pneumonia‐related death. Mold infection was the most common contributor to pneumonia‐related death in HSCT patients.     

A randomized trial of preemptive therapy for prevention of cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation

We studied the efficacy of two different doses of ganciclovir to prevent cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. We randomly assigned allogeneic HSCT recipients who had CMV infection to receive preemptive ganciclovir therapy with or without induction phase (5 mg/kg twice daily for 1 week). Thirty-two and thirty-six patients were randomized to the standard and the low-dose therapy group, respectively. The median time to CMV antigenemia or viremia clearance was 7 days (3–25 days) in the standard therapy group versus 11 days (3–69 days) in the low-dose therapy group (P = 0.540). The incidence of CMV disease was similar between the two groups (P = 0.366). The Kaplan–Meier estimate of event-free survival by day 180 after HSCT was 76.2% in the standard therapy group versus 66.7% in the low-dose therapy group (P = 0.590). Severe neutropenia (<0.5 × 10⁹/L) was observed in four (12.5%) patients in the standard therapy group versus two (5.6%) patients in the low-dose therapy group (P = 0.314). This study suggests that a low-dose ganciclovir preemptive therapy can be as effective as the standard-dose ganciclovir preemptive therapy for the prevention of CMV disease in allogeneic HSCT recipients.     

Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders

Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and are still unknown for activating KIR. The impact of activating KIR genotypes from donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft-versus-host disease (GVHD), relapse, survival or infections even in myeloid malignancies. However, additional activating KIR genes in the donor compared to the recipient's genotype or an identity between donor and recipient activating KIR genotypes was associated with a lower transplant-related mortality (TRM) (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28; P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.     

Haematopoietic stem cell transplantation for hepatitis-associated aplastic anaemia and non-hepatitis-associated aplastic anaemia: A propensity score-matched analysis

To validate the efficacy and safety of haematopoietic stem cell transplantation (HSCT) in hepatitis-associated aplastic anaemia (HAAA) patients, we reviewed 260 patients who underwent HSCT for acquired aplastic anaemia and eventually included 30 HAAA patients and 90 non-HAAA patients using propensity score matching. In the HAAA group, the estimated 5-year overall survival rate (75.8% vs. 86.5%, p = 0.409), failure-free survival (FFS) rate (74.0% vs. 83.2%, p = 0.485), graft-versus-host disease (GVHD)-free FFS rate (61.2% vs. 67.6%, p = 0.669) after HSCT were slightly lower but not statistically significant than those in the non-HAAA group. Both groups did not significantly differ in engraftment, post-transplant severe infection, cytomegalovirus (CMV) or Epstein-Barr virus viraemia, or GVHD incidences. The patterns of immune reconstitution were broadly consistent between the two groups. When stratifying HAAA patients according to donor type, no significant differences in survival, transplant-related mortality, or GVHD cumulative incidences were observed. CMV viraemia (68.7% vs 8.3%, p = 0.009) occurred more commonly in haploidentical donor (HID) transplants than in matched sibling donor transplants. However, early CMV disease incidence (5.6% vs. 0.0%, p = 1.000) was low. Overall, the post-transplant outcomes of HAAA patients were comparable to those of non-HAAA patients after balancing potential confounders, and HID-HSCT can offer an alternative curative option for HAAA.     

Surveillance of cytomegalovirus (CMV) DNAemia in pediatric allogeneic stem cell transplantation: incidence and outcome of CMV infection and disease.

Cytomegalovirus (CMV) remains a serious problem after hematopoietic stem cell transplantation (HSCT). To investigate the incidence of CMV infection and outcome we retrospectively analyzed 70 consecutive pediatric allogeneic HSCTs monitored by CMV polymerase chain reaction (PCR), with at least 1-year follow-up or until death. All patients at risk for CMV infection (CMV-seropositive patients and CMV-seronegative recipients transplanted from CMV-seropositive donors) received hyperimmune anti-CMV globulins whereas in the group of HSCT patients with both donor and recipient CMV negativity, polyvalent immunoglobulins were given, both at a dose of 400 mg/kg. All patients received acyclovir at prophylactic doses for at least 6 months. Patients were monitored twice a week by CMV PCR. Patients with 2 positive results for CMV DNAemia received ganciclovir for 14 days and continued until 2 consecutive negative results were obtained. The incidence of CMV DNAemia was 12.8% (9/70) in the whole group, with significant higher risk for patients with CMV-seropositive recipient status, 8 out of 22 (36%), vs. patients with seronegative status, 1 out of 48 (2%) (P=0.0002). Three out of 9 patients with DNAemia developed CMV disease despite adequate preemptive treatment. The transplant-related mortality was higher in the CMV-seropositive recipient group (P=0.05). Age, use of hyperimmune anti-CMV globulins at a high dose, and the low incidence of graft-versus-host disease might be contributing factors to this low incidence.     

Infectious complications associated with alemtuzumab use for allogeneic hematopoietic stem cell transplantation: comparison with anti-thymocyte globulin

Objectives. To evaluate the incidence of infectious complications after receiving alemtuzumab as part of a conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in Korean patients.
Methods. From November 2004 to January 2006, 12 patients who received alemtuzumab-based conditioning regimens for allogeneic HSCT were evaluated retrospectively until death or until the end of the follow-up in July 2007; they were compared with 18 patients who received rabbit anti-thymocyte globulin (ATG)-containing conditioning regimens from January 2002 to January 2006.
Results. Post-engraftment infections occurred more frequently in the alemtuzumab recipients than in the ATG recipients; the mean number of infections, excluding cytomegalovirus (CMV) infections, per patient during the follow-up period was 2.6±1.4 vs. 1.0±0.8 ( P =0.003), respectively. Although there was no statistical difference in the cumulative incidence of CMV  infection between the 2 groups (91.7% vs. 55.6%, P =0.381), the alemtuzumab recipients had a higher incidence of CMV  diseases (41.6% vs. 0%, P =0.0006) and a higher recurrence rate of CMV infection (90.0% vs. 27.3%, P =0.008) than did the ATG recipients, irrespective of the dose of alemtuzumab. Hemorrhagic cystitis (HC) (66.7% vs. 16.7%, P =0.009) and BK virus-associated HC (41.7% vs. 5.6%, P =0.026) developed more frequently in the alemtuzumab recipients. The all-cause mortality rate was not significantly different between the alemtuzumab and the ATG recipients (75% vs. 55.6%, P =0.28).
Conclusion. Alemtuzumab recipients had a high incidence of CMV disease as well as BK virus-associated HC compared with the ATG recipients. The dose of alemtuzumab should be tailored to patients' risk; in addition, the implementation of the appropriate prophylaxis for CMV and early detection strategies for BK virus are recommended.     

Use of NK cell activity in cure by transplant

Analogous to T cells, Natural Killer (NK) cells may facilitate engraftment, combat infection, and control cancer in bone marrow or haematopoietic stem cell transplantation (HSCT); however, NK cells do not cause graft-versus-host disease. Killer immunoglobulin-like receptors (KIRs) regulate NK cell function, and recent data suggest that KIR is as important as its ligand (human leucocyte antigen; HLA) in HSCT for both malignant and non-malignant conditions. Because there is substantial variability in KIR gene content, allelic polymorphism, and cell-surface expression among people, careful selection of donors based on HLA and KIR is essential to optimize HSCT outcomes. Furthermore, NK cells may be used for adoptive immunotherapy after HSCT in place of conventional donor lymphocyte infusion, as part of pre-transplant cytoreductive therapy, or as an independent therapeutic agent in high-risk leukaemia in place of sibling donor HSCT.     

隐匿性HBV感染无偿献血人群KIR基因多态性的特征分析

目的探讨无偿献血人群中隐匿性乙型肝炎病毒感染(OBI)献血者的KIR基因多态性及其特征分析。方法筛选2016年6月-2019年6月重庆市血液中心无偿献血人群中OBI献血者105例,采集外周血样提取DNA并作KIR基因分型;通过与国际等位基因网站公布的KIR基因型数据库对照分析,判断KIR基因型ID及单体型,计算基因表型频率(某种基因出现例数/总例数)、基因型频率(某中基因型出现例数/总例数)和基因频率(F)=√1-基因表型频率)。计数资料组间比较采用χ^2检验。结果105例OBI献血者均含有的KIR基因有2DL4、3DL2、3DL3和假基因3DP1;F>70%的KIR基因有2DL1、2DL3、3DL1、2DS4和假基因2DP1,其中KIR 2DS4第5外显子存在缺失的F为26.32%。F<30%的基因有2DL2、2DL5、2DS1、2DS2、2DS3、2DS5、3DS1。OBI献血人群分别与重庆汉族、河北汉族、江苏汉族和拉萨藏族比较,KIR 2DL3基因频率均降低(χ^2分别为9.598、12.236、13.719、10.974,P值均<0.05);OBI献血人群2DL2、2DL5、2DS2、2DS3与乌市维族比较差异均有统计学意义(χ2值分别为16.215、6.981、19.498、11.819,P值均<0.05);OBI献血人群2DL2、2DS1、2DS2、2DS3、2DS4与高加索人比较差异均有统计学意义(χ^2分别为22.477、3.877、34.937、6.909、4.271,P值均<0.05);OBI献血人群与重庆汉族相比,KIR 2DS4*del频率升高(χ^2=12.911,P<0.05)。OBI献血人群与长期慢性HBV感染组相比,2DS2、2DS3频率降低(χ^2分别为13.005、8.289,P值均<0.05),但2DS4、3DL1频率升高(χ^2分别10.032、3.865,P值均<0.05);OBI献血人群与强直性脊柱炎组相比,2DL3、2DS3基因频率降低(χ^2分别为7.851、16.504,P值均<0.05);OBI献血人群与男男同性恋HIV-AIDS组相比,2DS4、3DL1基因频率升高(χ^2分别为15.491、4.475,P<0.05);OBI献血人群与散发性急性戊型肝炎组相比,2DL1、2DL2、2DL3、2DL4、2DL5、2DS4、3DL2、3DL3、2DP1差异均有统计学意义(χ2分别为4.448、30.934、17.942、15.638、4.227、13.802、32.667、35.653、36.566,P值均<0.05)。共发现21种KIR基因型,其中基因型AA1(49.52%)最为常见,其次为BX2(18.1%)。结论OBI献血人群的KIR基因多态性具有自身特征,KIR 2DL3是OBI的潜在保护基因,KIR 2DS4*del则是OBI的潜在易感基因。