Infection transmission among lung transplant couples

The risk of transmission of infections in partnerships between 2 transplant recipients is unknown. The aim of this study was to evaluate transmission in such couples. In this single‐center study, lung transplant (LTx) couples were identified among outpatients between 1988 and 2016. Infection rates per year and survival were compared to matched LTx‐recipients not living in a transplant partnership. Twelve transplant couples were analyzed with cumulative 65 years of relationship. Overall infections were similar between LTx‐couples and matched LTx‐patients. No significant differences were noted in bacterial infections (.12 vs .27 per year), community‐acquired viral (CARV) infections (.26 vs .22 per year), rejection treatments (.22 vs .12 per year), or hospitalizations (.26 vs .46 per year) in transplant couples and matched controls, respectively. There was no transmission of any microbial colonization from 1 partner to the other. Five cases of simultaneously detected CARV infections occurred (metapneumovirus [3], H1N1 [1], and respiratory syncytial virus [RSV; 1]). Three couples exhibited cytomegalovirus (CMV) reactivation in both partners at the same time with confirmed seronegativity before transplantation. In this case series of 12 lung transplant couples, the partnerships between 2 transplant recipients have no greater risk of bacterial infection and colonization transmission in comparison with recipients not living in a transplant relationship. However, transplant couples should be informed about the risk for transmission of viral infections, which could impact the development of chronic lung allograft dysfunction (CLAD).     

超声斑点追踪技术监测心脏移植急性排斥反应一例

正监测和诊断急性排斥反应(acute rejection,AR)是监测心脏移植受者移植物功能的主要目的。本文通过对1例心脏移植受者应用超声斑点追踪技术监测并诊断AR,探讨评估总体纵向应变(global longitudinal strain,GLS)及总体圆周应变(global circumferential strain,GCS)作为无创监测与AR有关     

供者NK细胞及其嵌合状态在异基因造血干细胞移植中的研究进展

目前,异基因造血干细胞移植(allo-HSCT)已广泛应用于造血系统疾病的治疗,但移植术后也存在一系列并发症。NK细胞的运用为改善allo-HSCT受者预后带来希望,供者来源NK细胞通过其细胞膜上的杀伤细胞免疫球蛋白样受体与其配体错配发挥同种异体反应,该过程具有保留移植物抗白血病和减少移植物抗宿主病双重效应。NK细胞是allo-HSCT后受者体内最早重建的免疫细胞群,因此移植后供、受者NK细胞嵌合状态评估对预测疾病预后及指导干预治疗具有重要意义。基于NK细胞嵌合状态的供者NK细胞输注免疫干预疗法可改善疾病预后,在血液系统疾病治疗中表现出良好的应用前景。本文就近年来供者NK细胞及其嵌合状态在allo-HSCT中的研究进展作一综述。     

不同miR-146a表达条件下Treg细胞体内回输对小鼠心脏移植免疫排斥反应的影响

目的:本研究探讨调控miR-146a Treg细胞体内回输对小鼠心脏移植免疫排斥反应的影响。方法:流式分选Treg细胞并进行体外扩增。转染试剂分别上调和下调Treg miR-146a表达。建立小鼠心脏移植模型,设立对照组,空白Treg组,miR-146a上调组,miR-146a下调组。移植后回输Treg,观察生存曲线,病理分级,测定受体脾T细胞亚群,RT-PCR检测供心IFN-γ、IL-4、IL-17表达。结果:细胞扩增10倍后miR-146a表达无明显变化,并能有效调控miR-146a表达。回输后空白Treg组（中位生存期11 d）及上调组（中位生存期13 d）生存时间延长,病理分级降低（P<0.05）;上调组更为明显（P<0.05）;下调组（中位生存期7 d）生存时间缩短,病理分级升高（P<0.05）,Th1细胞数量（28.6%±2.7%）及供心IFN-γ表达（1.12±0.11）升高（P<0.05）。结论:体外能有效地分选和扩增Treg细胞,并保证miR-146a的表达。回输Treg明显抑制小鼠心脏移植急性排斥反应,上调组抑制功能增强,下调组抑制功能减弱。     

Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study

Rejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.     

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry

Sudden cardiac death (SCD) is responsible for ~10% of post‐heart transplant deaths. We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post‐transplant SCD. Adult heart transplant recipients (2004‐2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and Monte Carlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25 242 recipients. During a median follow‐up of 4.7 (2.3‐7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36‐2.31) and CAV (HR 3.32, 95% CI 2.73‐4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0‐4.6) and 5.4% (95% CI 3.8‐7.0), respectively, at 2 years from the CAV diagnosis, and 4.9% (95% CI 3.4‐6.5) and 8.0% (95% CI 6.1‐10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post‐transplant remains uncertain.     

Hybrid resistance to parental bone marrow grafts in nonlethally irradiated mice

Resistance to parental bone marrow (BM) grafts in F1 hybrid recipients is due to natural killer (NK) cell–mediated rejection triggered through “missing self” recognition. “Hybrid resistance” has usually been investigated in lethally irradiated F1 recipients in conjunction with pharmacological activation of NK cells. Here, we investigated BM‐directed NK‐cell alloreactivity in settings of reduced conditioning. Nonlethally irradiated (1‐3 Gy) or nonirradiated F1 (C57BL6 × BALB/c) recipient mice received titrated doses (5‐20 x 10⁶) of unseparated parental BALB/c BM without pharmacological NK cell activation. BM successfully engrafted in all mice and multilineage donor chimerism persisted long‐term (24 weeks), even in the absence of irradiation. Chimerism was associated with the rearrangement of the NK‐cell receptor repertoire suggestive of reduced reactivity to BALB/c. Chimerism levels were lower after transplantation with parental BALB/c than with syngeneic F1 BM, indicating partial NK‐mediated rejection of parental BM. Activation of NK cells with polyinosinic–polycytidylic acid sodium salt poly(I:C), reduced parental chimerism in nonirradiated BM recipients but did not prevent hematopoietic stem cell engraftment. In contrast, equal numbers of parental lymph node cells were completely rejected. Hence, hybrid resistance leads to incomplete rejection of parental BM under reduced conditioning settings.