IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury
IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury
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DOI：
10.1681/asn.2014111120
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发表时间：
2016-01-01
影响因子：
13.6
通讯作者：
Zeevi, Adriana
中科院分区：
文献类型：
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作者：
Lefaucheur, Carmen;Viglietti, Denis;Zeevi, Adriana
根据IgG亚类，抗体可具有不同的致病性。我们研究了循环中抗人HLA抗体的IgG亚类与抗体介导的同种异体肾移植损伤之间的关系。在2008年至2010年间进行的635例连续肾移植中，我们招募了125例在移植后第一年检测到供体特异性抗人HLA抗体（DSA）的患者。我们评估了DSA特征，包括特异性、HLA类特异性、平均荧光强度（MFI）、C1 q结合和IgG亚类以及血清评价时的移植物损伤表型。总体而言，51例（40.8%）患者发生急性抗体介导的排斥反应（aABMR），36例（28.8%）患者发生亚临床ABMR（sABMR），38例（30.4%）患者无ABMR。免疫显性DSA（iDSA，MFI水平最高的DSA）的MFI为6724 +/- 464，41.6%的患者iDSA显示C1 q阳性。iDSA IgG 1 -4亚类在人群中的分布分别为75.2%、44.0%、28.0%和26.4%。整合iDSA IgG亚类的无监督主成分分析显示，aABMR主要由IgG 3 iDSA驱动，而sABMR由IgG 4 iDSA驱动。IgG 3 iDSA与较短的排斥反应时间相关（P
Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51(40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724 +/- 464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P