PDF(Pubmed)
Abstract：
Circulating anti-HLA donor-specific antibodies (HLA-DSA) are often absent in kidney transplant recipients with microvascular inflammation (MVI). Missing self, the inability of donor endothelial cells to provide HLA I-mediated signals to inhibitory killer cell Ig-like receptors (KIRs) on recipient natural killer cells, can cause endothelial damage in vitro, and has been associated with HLA-DSA-negative MVI. However, missing self\'s clinical importance as a nonhumoral trigger of allograft rejection remains unclear.
In a population-based study of 924 consecutive kidney transplantations between March 2004 and February 2013, we performed high-resolution donor and recipient HLA typing and recipient KIR genotyping. Missing self was defined as the absence of A3/A11, Bw4, C1, or C2 donor genotype, with the presence of the corresponding educated recipient inhibitory KIR gene.
We identified missing self in 399 of 924 transplantations. Co-occurrence of missing self types had an additive effect in increasing MVI risk, with a threshold at two concurrent types (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.26 to 2.53), independent of HLA-DSA (HR, 5.65; 95% CI, 4.01 to 7.96). Missing self and lesions of cellular rejection were not associated. No HLA-DSAs were detectable in 146 of 222 recipients with MVI; 28 of the 146 had at least two missing self types. Missing self associated with transplant glomerulopathy after MVI (HR, 2.51; 95% CI, 1.12 to 5.62), although allograft survival was better than with HLA-DSA-associated MVI.
Missing self specifically and cumulatively increases MVI risk after kidney transplantation, independent of HLA-DSA. Systematic evaluation of missing self improves understanding of HLA-DSA-negative MVI and might be relevant for improved diagnostic classification and patient risk stratification.
In a population-based study of 924 consecutive kidney transplantations between March 2004 and February 2013, we performed high-resolution donor and recipient HLA typing and recipient KIR genotyping. Missing self was defined as the absence of A3/A11, Bw4, C1, or C2 donor genotype, with the presence of the corresponding educated recipient inhibitory KIR gene.
We identified missing self in 399 of 924 transplantations. Co-occurrence of missing self types had an additive effect in increasing MVI risk, with a threshold at two concurrent types (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.26 to 2.53), independent of HLA-DSA (HR, 5.65; 95% CI, 4.01 to 7.96). Missing self and lesions of cellular rejection were not associated. No HLA-DSAs were detectable in 146 of 222 recipients with MVI; 28 of the 146 had at least two missing self types. Missing self associated with transplant glomerulopathy after MVI (HR, 2.51; 95% CI, 1.12 to 5.62), although allograft survival was better than with HLA-DSA-associated MVI.
Missing self specifically and cumulatively increases MVI risk after kidney transplantation, independent of HLA-DSA. Systematic evaluation of missing self improves understanding of HLA-DSA-negative MVI and might be relevant for improved diagnostic classification and patient risk stratification.
摘要：
在患有微血管炎症（MVI）的肾移植受者中，循环抗HLA供体特异性抗体（HLA-DSA）通常不存在。想念自己，供体内皮细胞无法向受体自然杀伤细胞上的抑制性杀伤细胞Ig样受体（KIRs）提供HLAI介导的信号，会在体外引起内皮损伤，并与HLA-DSA阴性MVI相关。然而,缺失自我作为同种异体移植排斥反应的非体液触发因素的临床重要性尚不清楚。
在2004年3月至2013年2月期间924例连续肾移植的基于人群的研究中，我们进行了高分辨率供体和受体HLA分型和受体KIR基因分型。自我缺失定义为缺乏A3/A11，Bw4，C1或C2供体基因型，存在相应的受教育者抑制性KIR基因。
我们在924次移植中的399次中发现了自我缺失。同时出现的缺失自我类型在增加MVI风险方面具有累加效应，具有两种并发类型的阈值(危险比[HR]，1.78；95%置信区间[95%CI]，1.26to2.53),独立于HLA-DSA(HR，5.65；95%CI，4.01至7.96）。自我缺失和细胞排斥反应的损伤没有相关性。在222名患有MVI的接受者中，有146名未检测到HLA-DSA；146人中有28名至少有两种缺失的自身类型。MVI后与移植肾小球病相关的自我缺失(HR，2.51；95%CI，1.12至5.62)，尽管同种异体移植存活率优于HLA-DSA相关MVI。
自我特异性缺失和累积性缺失会增加肾移植后的MVI风险，独立于HLA-DSA。对缺失自我的系统评估可以提高对HLA-DSA阴性MVI的理解，并且可能与改进的诊断分类和患者风险分层有关。
在2004年3月至2013年2月期间924例连续肾移植的基于人群的研究中，我们进行了高分辨率供体和受体HLA分型和受体KIR基因分型。自我缺失定义为缺乏A3/A11，Bw4，C1或C2供体基因型，存在相应的受教育者抑制性KIR基因。
我们在924次移植中的399次中发现了自我缺失。同时出现的缺失自我类型在增加MVI风险方面具有累加效应，具有两种并发类型的阈值(危险比[HR]，1.78；95%置信区间[95%CI]，1.26to2.53),独立于HLA-DSA(HR，5.65；95%CI，4.01至7.96）。自我缺失和细胞排斥反应的损伤没有相关性。在222名患有MVI的接受者中，有146名未检测到HLA-DSA；146人中有28名至少有两种缺失的自身类型。MVI后与移植肾小球病相关的自我缺失(HR，2.51；95%CI，1.12至5.62)，尽管同种异体移植存活率优于HLA-DSA相关MVI。
自我特异性缺失和累积性缺失会增加肾移植后的MVI风险，独立于HLA-DSA。对缺失自我的系统评估可以提高对HLA-DSA阴性MVI的理解，并且可能与改进的诊断分类和患者风险分层有关。
