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

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 import...

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Bibliographic Details
Published in:Transplant infectious disease 2013-10, Vol.15 (5), p.533-539
Main Authors: Koldehoff, M., Beelen, D.W., Elmaagacli, A.H.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
allogeneic transplantation
Aspergillosis - epidemiology
Aspergillosis - etiology
Aspergillosis - genetics
Aspergillosis - immunology
Aspergillus
Aspergillus - isolation & purification
Female
Genes
Genetic Variation
Genotype
Hematopoietic Stem Cell Transplantation - adverse effects
HSCT
Humans
Immunocompromised Host
Immunologic Deficiency Syndromes
Immunology
Incidence
invasive aspergillosis
Leukemia - complications
Male
Middle Aged
Polymorphism, Single Nucleotide - genetics
Signal Transduction
SNP
Stem cells
TLR4
Toll-Like Receptor 4 - genetics
Transplants & implants
Young Adult
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Summary: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.
ISSN:1398-2273
1399-3062
DOI:10.1111/tid.12115