Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14

S. M. Palmer, Walter Klimecki, L. Yu, N. L. Reinsmoen, L. D. Snyder, T. M. Ganous, L. Burch, D. A. Schwartz

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

We have developed the hypothesis that genetic polymorphisms which alter the expression or function of innate immune receptors contribute to the marked interindividual differences in the onset and severity of lung transplant rejection. In this analysis, we considered the effects of a common promotor polymorphism of the lipopolysaccharide receptor CD14 associated with increased transcriptional activity upon the development of posttransplant rejection and graft survival. Genotyping was performed in 226 lung transplant recipients well characterized with regards to clinical outcomes. An earlier onset of acute rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft survival due to greater BOS related deaths was evident in patients with the CD14 -159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95% CI, 1.03-2.64, p-value = 0.04) after adjusting for other important covariates. Furthermore, TT patients have significantly greater sCD14, TNF-α and IFN-γ in the peripheral blood implying a heightened state of innate immune activation drives the development of increased post-transplant rejection. Inhibition of innate immune activation through CD14 represents a novel and potentially important therapeutic target to prevent post-transplant rejection and improve outcomes after human lung transplantation.

Original languageEnglish (US)
Pages (from-to)693-699
Number of pages7
JournalAmerican Journal of Transplantation
Volume7
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Lung Transplantation
Graft Rejection
Graft Survival
Bronchiolitis Obliterans
Survival
Genotype
CD14 Antigens
Lung
Genetic Polymorphisms
Proportional Hazards Models
Therapeutics

Keywords

  • Allograft rejection
  • CD14
  • Innateimmunity
  • Lung transplant

ASJC Scopus subject areas

  • Immunology

Cite this

Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. / Palmer, S. M.; Klimecki, Walter; Yu, L.; Reinsmoen, N. L.; Snyder, L. D.; Ganous, T. M.; Burch, L.; Schwartz, D. A.

In: American Journal of Transplantation, Vol. 7, No. 3, 03.2007, p. 693-699.

Research output: Contribution to journalArticle

Palmer, S. M. ; Klimecki, Walter ; Yu, L. ; Reinsmoen, N. L. ; Snyder, L. D. ; Ganous, T. M. ; Burch, L. ; Schwartz, D. A. / Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. In: American Journal of Transplantation. 2007 ; Vol. 7, No. 3. pp. 693-699.
@article{5a1a3d435512491f858a8ada7623e05a,
title = "Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14",
abstract = "We have developed the hypothesis that genetic polymorphisms which alter the expression or function of innate immune receptors contribute to the marked interindividual differences in the onset and severity of lung transplant rejection. In this analysis, we considered the effects of a common promotor polymorphism of the lipopolysaccharide receptor CD14 associated with increased transcriptional activity upon the development of posttransplant rejection and graft survival. Genotyping was performed in 226 lung transplant recipients well characterized with regards to clinical outcomes. An earlier onset of acute rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft survival due to greater BOS related deaths was evident in patients with the CD14 -159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95{\%} CI, 1.03-2.64, p-value = 0.04) after adjusting for other important covariates. Furthermore, TT patients have significantly greater sCD14, TNF-α and IFN-γ in the peripheral blood implying a heightened state of innate immune activation drives the development of increased post-transplant rejection. Inhibition of innate immune activation through CD14 represents a novel and potentially important therapeutic target to prevent post-transplant rejection and improve outcomes after human lung transplantation.",
keywords = "Allograft rejection, CD14, Innateimmunity, Lung transplant",
author = "Palmer, {S. M.} and Walter Klimecki and L. Yu and Reinsmoen, {N. L.} and Snyder, {L. D.} and Ganous, {T. M.} and L. Burch and Schwartz, {D. A.}",
year = "2007",
month = "3",
doi = "10.1111/j.1600-6143.2007.01669.x",
language = "English (US)",
volume = "7",
pages = "693--699",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14

AU - Palmer, S. M.

AU - Klimecki, Walter

AU - Yu, L.

AU - Reinsmoen, N. L.

AU - Snyder, L. D.

AU - Ganous, T. M.

AU - Burch, L.

AU - Schwartz, D. A.

PY - 2007/3

Y1 - 2007/3

N2 - We have developed the hypothesis that genetic polymorphisms which alter the expression or function of innate immune receptors contribute to the marked interindividual differences in the onset and severity of lung transplant rejection. In this analysis, we considered the effects of a common promotor polymorphism of the lipopolysaccharide receptor CD14 associated with increased transcriptional activity upon the development of posttransplant rejection and graft survival. Genotyping was performed in 226 lung transplant recipients well characterized with regards to clinical outcomes. An earlier onset of acute rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft survival due to greater BOS related deaths was evident in patients with the CD14 -159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95% CI, 1.03-2.64, p-value = 0.04) after adjusting for other important covariates. Furthermore, TT patients have significantly greater sCD14, TNF-α and IFN-γ in the peripheral blood implying a heightened state of innate immune activation drives the development of increased post-transplant rejection. Inhibition of innate immune activation through CD14 represents a novel and potentially important therapeutic target to prevent post-transplant rejection and improve outcomes after human lung transplantation.

AB - We have developed the hypothesis that genetic polymorphisms which alter the expression or function of innate immune receptors contribute to the marked interindividual differences in the onset and severity of lung transplant rejection. In this analysis, we considered the effects of a common promotor polymorphism of the lipopolysaccharide receptor CD14 associated with increased transcriptional activity upon the development of posttransplant rejection and graft survival. Genotyping was performed in 226 lung transplant recipients well characterized with regards to clinical outcomes. An earlier onset of acute rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft survival due to greater BOS related deaths was evident in patients with the CD14 -159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95% CI, 1.03-2.64, p-value = 0.04) after adjusting for other important covariates. Furthermore, TT patients have significantly greater sCD14, TNF-α and IFN-γ in the peripheral blood implying a heightened state of innate immune activation drives the development of increased post-transplant rejection. Inhibition of innate immune activation through CD14 represents a novel and potentially important therapeutic target to prevent post-transplant rejection and improve outcomes after human lung transplantation.

KW - Allograft rejection

KW - CD14

KW - Innateimmunity

KW - Lung transplant

UR - http://www.scopus.com/inward/record.url?scp=33847742648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847742648&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2007.01669.x

DO - 10.1111/j.1600-6143.2007.01669.x

M3 - Article

C2 - 17217435

AN - SCOPUS:33847742648

VL - 7

SP - 693

EP - 699

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 3

ER -