title: Increased susceptibility for aspergillosis and post-transplant immune deficiency in patients with gene variants of TLR4 after stem cell transplantation.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  These findings reinforce the importance of genetic variants in innate immunity and IA among the recipients of allogeneic HSCT.
authors.affiliation: Department of Bone Marrow Transplantation, West German Cancer Center, Medical School of University of Duisburg-Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Koldehoff
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
authors.forename: A H
authors.initials: AH
authors.lastname: Elmaagacli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001228:Aspergillosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D001230:Aspergillus / Q000302:isolation & purification*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes; D015994:Incidence; D007938:Leukemia / Q000150:complications; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: HSCT; SNP; TLR4; allogeneic transplantation; invasive aspergillosis