Molecular profiling of anemia in acute renal allograft rejection using DNA microarrays.
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.
Chua
Mei-Sze
MS
Department of Pediatrics, Stanford University School of Medicine, CCSR, Stanford CA, USA.
Barry
Christopher
C
Chen
Xin
X
Salvatierra
Oscar
O
Sarwal
Minnie M
MM
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000276:immunology / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005979:Glutathione Peroxidase / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
D001798:Blood Proteins; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; C089465:MPP1 protein, human; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C038340:lactoferrin receptors; D006418:Heme; D005979:Glutathione Peroxidase; D000624:5-Aminolevulinate Synthetase