Skip to main content
Journal cover image

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

Publication ,  Journal Article
Palmer, SM; Klimecki, W; Yu, L; Reinsmoen, NL; Snyder, LD; Ganous, TM; Burch, L; Schwartz, DA
Published in: Am J Transplant
March 2007

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-alpha and IFN-gamma 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.

Duke Scholars

Published In

Am J Transplant

DOI

ISSN

1600-6135

Publication Date

March 2007

Volume

7

Issue

3

Start / End Page

693 / 699

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Toll-Like Receptor 4
  • Surgery
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Lung Transplantation
  • Lung
  • Lipopolysaccharide Receptors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Palmer, S. M., Klimecki, W., Yu, L., Reinsmoen, N. L., Snyder, L. D., Ganous, T. M., … Schwartz, D. A. (2007). Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. Am J Transplant, 7(3), 693–699. https://doi.org/10.1111/j.1600-6143.2007.01669.x
Palmer, S. M., W. Klimecki, L. Yu, N. L. Reinsmoen, L. D. Snyder, T. M. Ganous, L. Burch, and D. A. Schwartz. “Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14.Am J Transplant 7, no. 3 (March 2007): 693–99. https://doi.org/10.1111/j.1600-6143.2007.01669.x.
Palmer SM, Klimecki W, Yu L, Reinsmoen NL, Snyder LD, Ganous TM, et al. Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. Am J Transplant. 2007 Mar;7(3):693–9.
Palmer, S. M., et al. “Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14.Am J Transplant, vol. 7, no. 3, Mar. 2007, pp. 693–99. Pubmed, doi:10.1111/j.1600-6143.2007.01669.x.
Palmer SM, Klimecki W, Yu L, Reinsmoen NL, Snyder LD, Ganous TM, Burch L, Schwartz DA. Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. Am J Transplant. 2007 Mar;7(3):693–699.
Journal cover image

Published In

Am J Transplant

DOI

ISSN

1600-6135

Publication Date

March 2007

Volume

7

Issue

3

Start / End Page

693 / 699

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Toll-Like Receptor 4
  • Surgery
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Lung Transplantation
  • Lung
  • Lipopolysaccharide Receptors