|
Title
|
|
|
|
A promoter polymorphism in the CD59 complement regulatory protein gene in donor lungs correlates with a higher risk for chronic rejection after lung transplantation
|
|
|
Author
|
|
|
|
|
|
|
Abstract
|
|
|
|
| Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p=0.016) and monocytes (p=0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL-6 (p=0.047) and fibroblast growth factor (p=0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody-mediated complement lysis (p<0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long-term survival (p=0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p=0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation. |
|
|
|
Language
|
|
|
|
English
|
|
|
Source (journal)
|
|
|
|
American journal of transplantation. - Copenhagen
|
|
|
Publication
|
|
|
|
Copenhagen
:
2016
|
|
|
ISSN
|
|
|
|
1600-6135
|
|
|
DOI
|
|
|
|
10.1111/AJT.13497
|
|
|
Volume/pages
|
|
|
|
16
:3
(2016)
, p. 987-998
|
|
|
ISI
|
|
|
|
000371240500031
|
|
|
Full text (Publisher's DOI)
|
|
|
|
|
|
|
Full text (publisher's version - intranet only)
|
|
|
|
|
|