Increased susceptibility for aspergillosis and post-transplant immune deficiency in patients with gene variants of TLR4 after stem cell transplantation

Transpl Infect Dis. 2013 Oct;15(5):533-9. doi: 10.1111/tid.12115. Epub 2013 Jul 25.


Introduction: Toll-like receptors (TLRs) detect invading pathogens through several pattern-recognition mechanisms and play a central role in the regulation of the immune system. In allogeneic hematopoietic stem cell transplantation (HSCT), the frequent opportunistic fungal infections remain an important cause of mortality and morbidity in these highly immunocompromised patients.

Methods: We analyzed 154 patients after allogeneic HSCT for acute leukemia for TLR4 gene variants 1063A/G (D299G) and 1363C/T (T399I) with their respective donors, and correlated the results with the incidence of invasive aspergillosis (IA) infection after transplant.

Results: Probable and proven IA in recipients was significantly increased if either recipients or donors exhibited one of the two TLR4 gene variants. In addition, recipients with TLR gene variants and IA showed a delayed T cell and NKT cell immune reconstitution after transplant. Increased susceptibility for IA was not associated with an increased rate of death-in-remission or decreased estimate for overall survival.

Conclusion: These findings reinforce the importance of genetic variants in innate immunity and IA among the recipients of allogeneic HSCT.

Keywords: HSCT; SNP; TLR4; allogeneic transplantation; invasive aspergillosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aspergillosis / epidemiology
  • Aspergillosis / etiology
  • Aspergillosis / genetics*
  • Aspergillosis / immunology
  • Aspergillus / isolation & purification*
  • Female
  • Genetic Variation
  • Genotype
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunocompromised Host
  • Immunologic Deficiency Syndromes
  • Incidence
  • Leukemia / complications
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics*
  • Young Adult


  • TLR4 protein, human
  • Toll-Like Receptor 4

Supplementary concepts

  • Immune Deficiency Disease