The molecular phenotypes of rejection in kidney transplant biopsies.
Curr Opin Organ Transplant
; 20(3): 359-67, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25944235
ABSTRACT
PURPOSE OF REVIEW The recent emergence of a system for distinguishing T-cell-mediated rejection (TCMR) from antibody-mediated rejection (ABMR), including C4d-negative ABMR, allows us to map the molecular features of these conditions. RECENT FINDINGS:
The TCMR landscape is dominated by molecules expressed in effector T cells, antigen-presenting cells (macrophages, dendritic cells, B cells) and interferon-gamma (IFNG)-induced genes. A surprising finding is the association of transcripts for inhibitory molecules such as CTLA4 and PDL1 with TCMR, indicating that this tubulo-interstitial inflammatory compartment is actively controlled. ABMR is dominated by endothelial transcripts related to angiogenesis, reflecting endothelial injury; natural killer (NK)-cell transcripts; and selected IFNG-regulated transcripts. This suggests a cognate unit of NK cells engaging donor-specific antibody bound to donor human leukocyte antigen antigens through their CD16a (FCGR3A) Fc receptors, triggering IFNG release. TCMR and ABMR share many rejection-associated transcripts, mainly IFNG-induced genes and transcripts shared between NK cells and CD8 effector T cells (e.g., KLRD1). In addition, acute kidney injury transcripts, which reflect the parenchymal response to injury, are shared between different forms of rejection and are indicative of disease progression.SUMMARY:
Microarray assessment provides a new dimension in biopsy assessment for diagnosis that offers mechanistic insights and sometimes challenges histology assessments.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
/
Rejeição de Enxerto
Limite:
Humans
Idioma:
En
Revista:
Curr Opin Organ Transplant
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Canadá