Molecular profiling of anemia in acute renal allograft rejection

Compromised renal function after renal allograft transplantation often results in anemia in the recipient. Molecular mechanisms leading to anemia during acute rejection are not fully understood; inadequate erythropoietin production and iron deficiency have been reported to be the main contributors. To increase our understanding of the molecular events underlying anemia in acute rejection, we analyzed the gene expression profiles of peripheral blood lymphocytes (PBL) from four pediatric renal allograft recipients with acute rejection and concurrent anemia, using DNA microarrays containing 9000 human cDNA clones (representing 7469 unique genes). In these anemic rejecting patients, an 'erythropoiesis cluster' of 11 down-regulated genes was identified, involved in hemoglobin transcription and synthesis, iron and folate binding and transport. Additionally, some alloimmune response genes were simultaneously down-regulated. An independent data set of 36 PBL samples, some with acute rejection and some with concurrence of acute rejection and anemia, were analyzed to support a possible association between acute rejection and anemia. In conclusion, analysis using DNA microarrays has identified a cluster of genes related to hemoglobin synthesis and/or erythropoeisis that was altered in kidneys with renal allograft rejection compared with normal kidneys. The possible relationship between alterations in the expression of this cluster, reduced renal function, the alloimmune process itself, and other influences on the renal transplant awaits further analysis. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design Using regression correlation

肾移植（renal allograft transplantation）术后肾功能不全（compromised renal function）常导致受者发生贫血（anemia）。目前急性排斥反应（acute rejection）引发贫血的分子机制尚未完全阐明；促红细胞生成素（erythropoietin）生成不足与缺铁（iron deficiency）被报道为主要致病因素。为加深对急性排斥反应伴发贫血的分子事件的理解，我们利用包含9000个人类cDNA克隆（cDNA clones，对应7469个独特基因）的DNA微阵列（DNA microarrays），对4例合并急性排斥反应与贫血的儿童肾移植受者的外周血淋巴细胞（peripheral blood lymphocytes, PBL）进行基因表达谱分析。在该类贫血伴排斥反应的患者中，我们鉴定出11个表达下调的红细胞生成相关基因簇（erythropoiesis cluster），其功能涉及血红蛋白转录与合成、铁与叶酸结合及转运。另有部分同种免疫应答（alloimmune response）相关基因同时出现表达下调。我们对包含36份PBL样本的独立数据集进行了分析，其中部分样本仅伴急性排斥反应，部分同时合并急性排斥反应与贫血，以验证急性排斥反应与贫血间可能存在的关联。综上，通过DNA微阵列分析，我们发现相较于正常肾脏组织，发生肾移植排斥反应的肾脏中存在一组与血红蛋白合成及/或红细胞生成相关的基因表达异常。该基因簇的表达改变与肾功能减退、同种免疫应答过程及其他肾移植相关影响因素之间的潜在关联，仍有待进一步研究阐明。本研究属于疾病状态实验设计类型，即针对感染、病理状态、综合征等各类疾病状态展开研究。关键词：disease_state_design 采用回归相关分析