Intragraft gene expression in positive crossmatch kidney allografts: ongoing inflammation mediates chronic antibody-mediated injury.
Am J Transplant
; 12(6): 1551-63, 2012 Jun.
Article
in En
| MEDLINE
| ID: mdl-22335458
ABSTRACT
We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR were performed on RNA from protocol renal allograft biopsies in three groups (1) +XM/TG+ biopsies before and after TG; (2) +XM/NoTG; and (3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2447 genes (18%) and 3200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3718 probe sets were differentially expressed but these were over-represented in only four pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to the +XM/NoTG and control groups. In conclusion, pretransplant donor-specific anti-HLA antibodies results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of +XM grafts are exposed to chronic injury.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression
/
Kidney Transplantation
/
Antibodies
Type of study:
Guideline
Limits:
Humans
Language:
En
Journal:
Am J Transplant
Journal subject:
TRANSPLANTE
Year:
2012
Document type:
Article
Affiliation country:
Estados Unidos