The clinical and genomic significance of donor-specific antibody (DSA) positive/C4d negative and DSA negative/C4d negative transplant glomerulopathy. Homo sapiens

We investigated the clinical, histopathologic and genomic features of donor-specific antibody (DSA) +/C4d- and DSA-/C4d- transplant glomerulopathy (TGP) using microarrays. Comparison of the gene expression profiles of DSA-/C4d- TGP biopsies with ptc+g score > 1 to normal and IFTA (Interstitial Fibrosis and Tubular Atrophy) biopsies by microarrays revealed increased expression of quantitative cytotoxic T cell--associated transcripts (QCAT). However, CAMR (chronic antibody-mediated rejection) and DSA+/C4d- TGP had increased expression of QCAT, interferon-gamma and rejection induced, constitutive macrophage-associated, natural killer cell-associated, and DSA selective transcripts. B cell and endothelial cell associated transcripts expression were upregulated only in CAMR biopsies. Our results suggest that while DSA+/C4d- TGP should be classified under CAMR, DSA-/C4d- TGP with ptc+g score > 1 probably develops through a chronic cellular immune response. Overall design: Total of 57 arrays included in this study. G1. Normal transplant kidney biopsies (N= 12); G2. Non-specific IFTA (N= 17); G3. TGP DSA-/C4d- (N=8); G4. TGP DSA+/C4d- (N= 9); G5. CAMR/TGP C4d+/DSA+ (N= 11)

本研究采用基因芯片（microarrays）技术，分析了供体特异性抗体（Donor-specific antibody, DSA）阳性/C4d阴性以及DSA阴性/C4d阴性的移植肾小球病（Transplant glomerulopathy, TGP）的临床、组织病理与基因组特征。通过基因芯片对比ptc+g评分＞1的DSA阴性/C4d阴性TGP活检样本、正常肾移植活检样本与间质纤维化及肾小管萎缩（Interstitial Fibrosis and Tubular Atrophy, IFTA）活检样本的基因表达谱，发现定量细胞毒性T细胞相关转录本（Quantitative Cytotoxic T cell-associated Transcripts, QCAT）的表达水平显著升高。然而，慢性抗体介导性排斥反应（Chronic Antibody-mediated Rejection, CAMR）与DSA阳性/C4d阴性TGP样本中，QCAT、干扰素-γ、排斥诱导型固有巨噬细胞相关、自然杀伤细胞相关及DSA选择性转录本的表达水平均显著上调。仅在CAMR活检样本中，B细胞与内皮细胞相关转录本的表达水平出现上调。本研究结果提示，尽管DSA阳性/C4d阴性TGP应归类于CAMR范畴，但ptc+g评分＞1的DSA阴性/C4d阴性TGP可能通过慢性细胞免疫应答途径发病。实验整体设计：本研究共纳入57份芯片样本，分组如下：G1组：正常肾移植活检样本（N=12）；G2组：非特异性IFTA活检样本（N=17）；G3组：DSA阴性/C4d阴性TGP样本（N=8）；G4组：DSA阳性/C4d阴性TGP样本（N=9）；G5组：CAMR/TGP C4d阳性/DSA阳性样本（N=11）