The Molecular Landscape of Antibody-Mediated Kidney Transplant Rejection: Evidence for NK Involvement Through XXXX a Fc Receptors.

@entity35424 @entity137 @entity3545 @entity14539 @entity71310 @entity71311 @entity379 @entity4071 @entity20363 @entity20197 @entity372 @entity130 @entity436
UNASSIGNED: The recent recognition that antibody-mediated rejection (ABMR) is the major cause of kidney transplant loss creates strong interest in its pathogenesis. We used microarray analysis of kidney transplant biopsies to identify the changes in pure ABMR. We found that the ABMR transcript changes in the initial Discovery Set were strongly conserved in a subsequent Validation Set. In the Combined Set of 703 biopsies, 2603 transcripts were significantly changed (FDR   <   0.05) in ABMR versus all other biopsies. In cultured cells, the transcripts strongly associated with ABMR were expressed in endothelial cells, e.g. cadherins @entity3545 and @entity20197 ; @entity379 -treated endothelial cells, e.g. phospholipase @entity71310 and chemokine @entity372 ; or NK cells, e.g. @entity137 molecules granulysin ( @entity35424 ) and @entity71311 . Other ABMR transcripts were expressed in normal kidney but not cell lines, either increased e.g. Duffy @entity436 ( @entity20363 ) or decreased e.g. sclerostin ( @entity14539 ). Pathway analysis of ABMR transcripts identified angiogenesis, with roles for angiopoietin and vascular endothelial growth factors; leukocyte-endothelial interactions; and NK signaling, including evidence for @entity4071 a Fc receptor signaling elements shared with T cells. These data support a model of ABMR involving @entity130 in the microcirculation induced by cognate recognition involving antibody and @entity4071 , triggering @entity379 release and antibody-dependent NK cell-mediated @entity137 .
