Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection

作者：Sis Banu^*; Halloran Philip F

来源：Current Opinion in Organ Transplantation, 2010, 15(1): 42-48.

DOI：10.1097/MOT.0b013e3283352a50

• antibody-mediated rejection
• C4d
• donor-specific antibody
• endothelial gene expression
• microarrays

Purpose of review
In the last decade, there has been a growing recognition of alloantibody responses in organ transplantation, but phenotypes related to anti body-mediated rejection (ABMR) remain incompletely defined. This article reviews recent molecular studies in kidney allograft tissues that decipher molecular burden and mechanisms of ABMR, leading to discovery of a new phenotype: 'C4d-negative ABMR'.
Recent findings
High endothelial gene expression in kidney transplant biopsies with anti-human leukocyte antigen alloantibody indicates active anti body-mediated damage and poor graft survival, defining a previously unknown group of C4d-negative ABMR. C4d-negative ABMR is characterized by high intragraft endothelial gene expression, alloantibodies, histology of chronic ABMR (less frequently acute ABMR), and poor outcomes. Thus, endothelial molecular phenotype in biopsies with circulating antibody detects degree of active graft injury, and many of these transcripts reflect endothelial activation. C4d-negative ABMR is twice as common as C4d-positive ABMR. Recognition of this new phenotype reveals ABMR (C4d positive or negative) as the most common cause of late kidney transplant loss.
Summary
C4d staining, although very useful, is insensitive for detecting ABMR. Measuring endothelial gene expression in biopsies from kidneys with alloantibody is a sensitive and specific method to diagnose ABMR and predict graft outcomes.

• 出版日期2010-2